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Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.
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Infecções Bacterianas , Bacteriófagos , Terapia por Fagos , Animais , Humanos , Ratos , Infecções Bacterianas/terapia , Bacteriófagos/fisiologia , Mamíferos , Fagos de Pseudomonas , Distribuição Tecidual , Farmacorresistência Bacteriana MúltiplaRESUMO
MOTIVATION: Accumulating evidences have indicated that microRNA (miRNA) plays a crucial role in the pathogenesis and progression of various complex diseases. Inferring disease-associated miRNAs is significant to explore the etiology, diagnosis and treatment of human diseases. As the biological experiments are time-consuming and labor-intensive, developing effective computational methods has become indispensable to identify associations between miRNAs and diseases. RESULTS: We present an Ensemble learning framework with Resampling method for MiRNA-Disease Association (ERMDA) prediction to discover potential disease-related miRNAs. Firstly, the resampling strategy is proposed for building multiple different balanced training subsets to address the challenge of sample imbalance within the database. Then, ERMDA extracts miRNA and disease feature representations by integrating miRNA-miRNA similarities, disease-disease similarities and experimentally verified miRNA-disease association information. Next, the feature selection approach is applied to reduce the redundant information and increase the diversity among these subsets. Lastly, ERMDA constructs an individual learner on each subset to yield primitive outcomes, and the soft voting method is introduced for making the final decision based on the prediction results of individual learners. A series of experimental results demonstrates that ERMDA outperforms other state-of-the-art methods on both balanced and unbalanced testing sets. Besides, case studies conducted on the three human diseases further confirm the ERMDA's prediction capability for identifying potential disease-related miRNAs. In conclusion, these experimental results demonstrate that our method can serve as an effective and reliable tool for researchers to explore the regulatory role of miRNAs in complex diseases.
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Doença/genética , Estudos de Associação Genética , Aprendizado de Máquina , MicroRNAs/genética , Algoritmos , Biologia Computacional , Predisposição Genética para Doença/genética , HumanosRESUMO
Large-scale metabolomics is a powerful technique that has attracted widespread attention in biomedical studies focused on identifying biomarkers and interpreting the mechanisms of complex diseases. Despite a rapid increase in the number of large-scale metabolomic studies, the analysis of metabolomic data remains a key challenge. Specifically, diverse unwanted variations and batch effects in processing many samples have a substantial impact on identifying true biological markers, and it is a daunting challenge to annotate a plethora of peaks as metabolites in untargeted mass spectrometry-based metabolomics. Therefore, the development of an out-of-the-box tool is urgently needed to realize data integration and to accurately annotate metabolites with enhanced functions. In this study, the LargeMetabo package based on R code was developed for processing and analyzing large-scale metabolomic data. This package is unique because it is capable of (1) integrating multiple analytical experiments to effectively boost the power of statistical analysis; (2) selecting the appropriate biomarker identification method by intelligent assessment for large-scale metabolic data and (3) providing metabolite annotation and enrichment analysis based on an enhanced metabolite database. The LargeMetabo package can facilitate flexibility and reproducibility in large-scale metabolomics. The package is freely available from https://github.com/LargeMetabo/LargeMetabo.
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Metabolômica , Software , Reprodutibilidade dos Testes , Metabolômica/métodos , Espectrometria de Massas , BiomarcadoresRESUMO
MOTIVATION: CircularRNA (circRNA) is a class of noncoding RNA with high conservation and stability, which is considered as an important disease biomarker and drug target. Accumulating pieces of evidence have indicated that circRNA plays a crucial role in the pathogenesis and progression of many complex diseases. As the biological experiments are time-consuming and labor-intensive, developing an accurate computational prediction method has become indispensable to identify disease-related circRNAs. RESULTS: We presented a hybrid graph representation learning framework, named GraphCDA, for predicting the potential circRNA-disease associations. Firstly, the circRNA-circRNA similarity network and disease-disease similarity network were constructed to characterize the relationships of circRNAs and diseases, respectively. Secondly, a hybrid graph embedding model combining Graph Convolutional Networks and Graph Attention Networks was introduced to learn the feature representations of circRNAs and diseases simultaneously. Finally, the learned representations were concatenated and employed to build the prediction model for identifying the circRNA-disease associations. A series of experimental results demonstrated that GraphCDA outperformed other state-of-the-art methods on several public databases. Moreover, GraphCDA could achieve good performance when only using a small number of known circRNA-disease associations as the training set. Besides, case studies conducted on several human diseases further confirmed the prediction capability of GraphCDA for predicting potential disease-related circRNAs. In conclusion, extensive experimental results indicated that GraphCDA could serve as a reliable tool for exploring the regulatory role of circRNAs in complex diseases.
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Biologia Computacional , RNA Circular , Biomarcadores , Biologia Computacional/métodos , Humanos , PolímerosRESUMO
Long-term pure forest (PF) management and successive planting has result resulted in "low-efficiency artificial forests" in large areas. However, controversy persists over the promoting effect of introduction of broadleaf tree species on production efficiency of PF. This study hypothesised that introduced broadleaf tree species can significantly promote both water-nutrient use efficiency and gross primary productivity (GPP)of PF. Tree ring chronologies, water source, water use efficiency and GPP were analysed in coniferous Cunninghamia lanceolata and broadleaved Phoebe zhennan growing over the past three decades. The introduction of P. zhennan into C. lanceolata plantations resulted in inter-specific competition for water, probably because of the similarity of the main water source of these two tree species. However, C. lanceolata absorbed more water with a higher nutrient level from the 40-60-cm soil layer in mixed forests (MF). Although the co-existing tree species limited the basal area increment and growth rates of C. lanceolata in MF plots, the acquisition of dissolved nutrients from the fertile topsoil layer were enhanced; this increased the water use efficiency and GPP of MF plots. To achieve better ecological benefits and GPP, MFs should be constructed in southern China.
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The unique apical hook in dicotyledonous plants protects the shoot apical meristem and cotyledons when seedlings emerge through the soil. Its formation involves differential cell growth under the coordinated control of plant hormones, especially ethylene and auxin. Microtubules are essential players in plant cell growth that are regulated by multiple microtubule-associated proteins (MAPs). However, the role and underlying mechanisms of MAP-microtubule modules in differential cell growth are poorly understood. In this study, we found that the previously uncharacterized Arabidopsis MAP WAVE-DAMPENED2-LIKE4 (WDL4) protein plays a positive role in apical hook opening. WDL4 exhibits a temporal expression pattern during hook development in dark-grown seedlings that is directly regulated by ethylene signaling. WDL4 mutants showed a delayed hook opening phenotype while overexpression of WDL4 resulted in enhanced hook opening. In particular, wdl4-1 mutants exhibited stronger auxin accumulation in the concave side of the apical hook. Furthermore, the regulation of the auxin maxima and trafficking of the auxin efflux carriers PIN-FORMED1 (PIN1) and PIN7 in the hook region is critical for WDL4-mediated hook opening. Together, our study demonstrates that WDL4 positively regulates apical hook opening by modulating auxin distribution, thus unraveling a mechanism for MAP-mediated differential plant cell growth.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Ácidos Indolacéticos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Arabidopsis/citologia , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas Associadas aos Microtúbulos/genética , Células Vegetais , Plantas Geneticamente Modificadas , Transporte Proteico , Plântula/fisiologia , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.
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Antineoplásicos , Piridazinas , Piridazinas/química , Piridazinas/farmacologia , Piridazinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Relação Estrutura-Atividade , Química Farmacêutica , Estrutura Molecular , Neoplasias/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Sulfide solid electrolyte membranes employed in all-solid-state lithium batteries generally show high thickness and poor chemical stability, which limit the cell-level energy density and cycle life. In this work, Li9.88GeP1.96Sb0.04S11.88Cl0.12 solid electrolyte is synthesized with Sb, Cl partial substitution of P, S, possessing excellent toluene tolerance and stability to lithium. The formed SbS43- group in Li9.88GeP1.96Sb0.04S11.88Cl0.12 exhibits low adsorption energy and reactivity for toluene molecules, confirmed by first-principles density functional theory calculation. Using toluene as the solvent, ultrathin Li9.88GeP1.96Sb0.04S11.88Cl0.12 membranes with adjustable thicknesses can be well prepared by the wet coating method, and an 8 µm thick membrane exhibits an ionic conductivity of 1.9 mS cm-1 with ultrahigh ionic conductance of 1860 mS and ultralow areal resistance of 0.68 Ω cm-2 at 25 °C. The obtained LiCoO2|Li9.88GeP1.96Sb0.04S11.88Cl0.12 membrane|Li all-solid-state lithium battery shows an initial reversible capacity of 125.6 mAh g-1 with a capacity retention of 86.3% after 250 cycles at 0.1 C under 60 °C.
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The positive contributions of carriers to aerobic granulation have been wildly appreciated. In this study, as a way resource utilization, the dredged sediment was thermally-treated to prepared as carriers to promote aerobic granular sludge (AGS) formation and stability. The system was started under low superficial gas velocity (SGV, 0.6 cm/s)for a lower energy consumption. Two sequencing batch reactors (SBR) labeled R1 (no added carriers) and R2 (carriers added), were used in the experiment. R2 had excellent performance of granulation time (shortened nearly 43%). The maximum mean particle size at the maturity stage of AGS in R2 (0.545 mm) was larger compared to R1 (0.296 mm). The sludge settling performance in R2 was better. The reactors exhibited high chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) removal rates. The total phosphorus (TP) removal rate in R2 was higher than R1 (almost 15% higher) on stage II (93-175d). R2 had a higher microbial abundance and dominant bacteria content. The relative abundance of dominant species was mainly affected by the carrier. However, the enrichment of dominant microorganisms and the evolution of subdominant species were more influenced by the increase of SGV. The results indicated that the addition of carriers induced the secretion of extracellular polymeric substances (EPS) by microorganisms and accelerated the rapid formation of initial microbial aggregates. This work provided a low-cost method and condition to enhance aerobic granulation, which may be helpful in optimizing wastewater treatment processes.
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Reatores Biológicos , Esgotos , Eliminação de Resíduos Líquidos , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Fósforo , Análise da Demanda Biológica de Oxigênio , Nitrogênio , AerobioseRESUMO
Automatic detection of pulmonary nodule based on computer tomography (CT) images can significantly improve the diagnosis and treatment of lung cancer. However, there is a lack of effective interactive tools to record the marked results of radiologists in real time and feed them back to the algorithm model for iterative optimization. This paper designed and developed an online interactive review system supporting the assisted diagnosis of lung nodules in CT images. Lung nodules were detected by the preset model and presented to doctors, who marked or corrected the lung nodules detected by the system with their professional knowledge, and then iteratively optimized the AI model with active learning strategy according to the marked results of radiologists to continuously improve the accuracy of the model. The subset 5-9 dataset of the lung nodule analysis 2016(LUNA16) was used for iteration experiments. The precision, F1-score and MioU indexes were steadily improved with the increase of the number of iterations, and the precision increased from 0.213 9 to 0.565 6. The results in this paper show that the system not only uses deep segmentation model to assist radiologists, but also optimizes the model by using radiologists' feedback information to the maximum extent, iteratively improving the accuracy of the model and better assisting radiologists.
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Algoritmos , Diagnóstico por Computador , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Diagnóstico por Computador/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Aprendizado de MáquinaRESUMO
The limited oxidation stability of ether solvents has posed significant challenges for their applications in high-voltage lithium metal batteries (LMBs). To tackle this issue, the prevailing strategy either adopts a high concentration of fluorinated salts or relies on highly fluorinated solvents, which will significantly increase the manufacturing cost and create severe environmental hazards. Herein, an alternative and sustainable salt engineering approach is proposed to enable the utilization of dilute electrolytes consisting of fluorine (F)-free ethers in high-voltage LMBs. The proposed 0.8â M electrolyte supports stable lithium plating-stripping with a high Coulombic efficiency of 99.47 % and effectively mitigates the metal dissolution, phase transition, and gas release issues of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode upon charging to high voltages. Consequently, the 4.5â V high-loading Li||NCM 811â cell shows a capacity retention of 75.2 % after 300 cycles. Multimodal experimental characterizations coupled with theoretical investigations demonstrate that the boron-containing salt plays a pivotal role in forming the passivation layers on both anode and cathode. The present simple and cost-effective electrolyte design strategy offers a promising and alternative avenue for using commercially mature, environmentally benign, and low-cost F-free ethers in high-voltage LMBs.
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The intensity and frequency of droughts are projected to rise in recent years and adversely affect forests. Thus, information on plant water use and acclimation during and after droughts is crucial. This study used the stable isotope and thermal dissipation probes to detect the water-use adaptation of mixed forests to drought using a precipitation gradient control experiment in the field. The results showed that Platycladus orientalis and Quercus variabilis mainly absorbed stable water from deep soil layers during the drought (32.05% and 28.2%, respectively). The synergetic nocturnal sap flow in both species replenished the water loss, but P. orientalis experienced a greater decline in transpiration acclimation to drought. The transpiration of Q. variabilis remained high since it was mainly induced by radiation. After short-term exposure to drought, P. orientalis majorly obtained shallow soil water, confirming its sensitivity to shallow water. Contrarily, Q. variabilis mainly absorbed stable water from deep soil layers regardless of the soil water content. Therefore, these findings suggest that Q. variabilis cannot physiologically adjust to extreme drought events, possibly limiting their future distributions and altering the composition of boreal forests.
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Quercus , Árvores , Árvores/fisiologia , Resistência à Seca , Água/fisiologia , Solo , Florestas , SecasRESUMO
KEY MESSAGE: Genome-wide association mapping revealed a novel QTL for shoot length across multiple environments. Its causal gene, LOC_Os01g68500, was identified firstly through gene-based haplotype analysis, gene expression and knockout transgenic verification. Strong seedling vigor is an important breeding target for rice varieties used in direct seeding. Shoot length (SL) is one of the important traits associated with seedling vigor characterized by rapid growth of seedling, which enhance seedling emergence. Therefore, mining genes for SL and conducting molecular breeding help to develop varieties for direct seeding. However, few QTLs for SL have been fine mapped or cloned so far. In this study, a genome-wide association study of SL was performed in a diverse rice collection consisting of 391 accessions in two years, using phenotypes generated by different cultivation methods according to the production practice, and a total of twenty-four QTLs for SL were identified. Among them, the novel QTL qSL-1f on chromosome 1 could be stably detected across all three cultivation methods in the whole population and indica subpopulation. Through gene-based haplotype analysis of the annotated genes within the putative region of qSL-1f, and validated by gene expression and knockout transgenic experiments, LOC_Os01g68500 (i.e., Os01g0913100 in RAP-DB) was identified as the causal gene for SL, which has a single-base variation (C-to-A transversion) in its CDS region, resulting in the significant difference in SL of rice. LOC_Os01g68500 encodes a DUF538 (Domain of unknown function) containing protein, and the function of DUF538 protein gene on rice seedling growth is firstly reported in this study. These results provide a new clue for exploring the molecular mechanism regulating SL, and promising gene source for the molecular breeding in rice.
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Oryza , Oryza/genética , Estudo de Associação Genômica Ampla , Haplótipos , Melhoramento Vegetal , Mapeamento Cromossômico/métodos , Plântula/genéticaRESUMO
BACKGROUND: Fragrant rice is increasingly popular with the public owing to its fresh aroma, and 2-acetyl-1-pyrroline (2-AP) is the main characteristic component of the aroma in fragrant rice. Rice-fish co-culture is an environmentally friendly practice in sustainable agriculture. However, the effect of rice-fish co-culture on 2-AP in grains has received little study. A conventional fragrant rice (Meixiangzhan 2) was used, and a related field experiment during three rice growing seasons was conducted to investigate the effects of rice-fish co-culture on 2-AP, as well as the rice quality, yield, plant nutrients, and precursors and enzyme activities of 2-AP biosynthesis in leaves. This study involved three fish stocking density treatments (i.e. 9000 (D1), 15 000 (D2), and 21 000 (D3) fish fries per hectare) and rice monocropping. RESULTS: Rice-fish co-culture increased the 2-AP content in grains by 2.5-49.4% over that of the monocropping, with significant increases in the early and late rice seasons of 2020. Rice-fish co-culture treatments significantly promoted seed-setting rates by 3.39-7.65%, and improved leaf nutrients and rice quality. Notably, the D2 treatment significantly increased leaf total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents and the head rice rate at maturity stage, while significantly decreased chalkiness degree. There was no significant difference in rice yield. CONCLUSION: Rice-fish co-culture had positive effects on 2-AP synthesis, rice quality, seed-setting rates, and plant nutrient contents. The better stocking density of field fish for rice-fish co-culture in this study was 15 000 fish ha-1 . © 2023 Society of Chemical Industry.
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Oryza , Animais , Oryza/química , Grão Comestível , Sementes , PirróisRESUMO
Thallium contamination in water can cause great danger to the environment. In this study, we synthesized manganese oxide-coated sand (MOCS) and investigated the transport and retention behaviors of Tl(I) in MOCS under different conditions. Characterization methods combined with a two-site nonequilibrium transport model were applied to explore the retention mechanisms. The results showed that Tl(I) mobility was strongly inhibited in MOCS media, and the retention capacity calculated from the fitted model was 510.41 mg/g under neutral conditions. The retention process included adsorption and oxidative precipitation by the manganese oxides coated on the sand surface. Cotransport with the same concentration of Mn(II) led to halving Tl(I) retention due to competition for reactive sites. Enhanced Tl(I) retention was observed under alkaline conditions, as increasing pH promoted electronegativity on the media surface. Moreover, the competitive cation Ca2+ significantly weakened Tl(I) retention by occupying adsorption sites. These findings provide new insights into understanding Tl(I) transport behavior in water-saturated porous media and suggest that manganese oxide-coated sand can be a cost-effective filter media for treating Tl-contaminated water.
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Areia , Tálio , Tálio/análise , Óxidos/química , Água , Adsorção , Dióxido de Silício/químicaRESUMO
Glioma is a clinically heterogeneous disease with a poor prognosis. Berberine (BBR), as a multi-target anti-tumor alkaloid, has the ability to penetrate the blood-brain barrier and shows cytotoxicity to glioma cells. In previous studies, we demonstrated that berberine inhibits glioma cell proliferation by inhibiting mutant p53 protein and promoting mitochondrial damage. In addition, berberine has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on collagen in cancer needs to be further elucidated. In this study, we proved that the collagen XI alpha 1 chain (COL11A1) is highly expressed in glioma cell lines and associated with migration and invasion of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-ß1/COL11A1 pathway and changes actin cytoskeleton arrangement. Nude mouse subcutaneous xenografts model also showed that berberine inhibited the expression of COL11A1 in vivo. Collectively, berberine that targets COL11A1 to inhibit glioma migration and invasion, may serve as a promising candidate for the development of anti-glioma drugs in the future.
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Berberina , Glioma , Animais , Berberina/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colágeno/farmacologia , Colágeno Tipo XI , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Camundongos , Camundongos Nus , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The counteractive effect of atmospheric CO2 (ca ) enrichment and drought stress on tree growth results in great uncertainty in the growth patterns of forest plantations in cold semi-arid regions. We analysed tree ring chronologies and carbon isotopes in Populus simonii plantations in cold semi-arid areas in northern China over the past four decades. We hypothesized that the hydraulic stress from drought would override the stimulating effect of increasing ca and temperature (T) on stem growth (basal area increment [BAI]). We found the stimulating effect of rising ca and T on the growth, indicated by continuous increase of intrinsic water-use efficiency in all stands and a positive correlation between T and BAI. However, these effects failed to alleviate the negative impacts of drought on tree growth. Concurrent acceleration of BAI reversed during the intensive drought episodes. Water stress resulted from inaccessibility of roots to deep soil water rather than from lack of precipitation, suggested by the decoupling of BAI from precipitation and vapour pressure deficit. Local soil water limitation might also cause greater stomatal regulation in declining trees, indicated by lower intercellular CO2 concentration. Thus, site-specific soil moisture conditions growth sensitivity to global warming resulting in site-specific decline episodes in drought-prone areas.
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Populus , Dióxido de Carbono , Desidratação , Secas , Florestas , Solo , Temperatura , ÁrvoresRESUMO
Extracellular matrix (ECM) plays an important role in the progression of cancer. Collagen is the most abundant component in ECM, and it is involved in the biological formation of cancer. Although type XI collagen is a minor fibrillar collagen, collagen XI alpha 1 chain (COL11A1) has been found to be upregulated in a variety of cancers including ovarian cancer, breast cancer, thyroid cancer, pancreatic cancer, non-small-cell lung cancer, and transitional cell carcinoma of the bladder. High levels of COL11A1 usually predict poor prognosis, while COL11A1 is related to angiogenesis, invasion, and drug resistance of cancer. However, little is known about the specific mechanism by which COL11A1 regulates tumor progression. Here, we have organized and summarized the recent developments regarding elucidation of the relationship between COL11A1 and various cancers, as well as the interaction between COL11A1 and intracellular signaling pathways. In addition, we have selected therapeutic agents targeting COL11A1. All these indicate the possibility of using COL11A1 as a target for cancer treatment.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Colágeno Tipo XI/antagonistas & inibidores , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Contamination of microplastics (MPs) is a global environmental issue that has received much attention from the scientific and public communities due to ecological concerns in recent decades. Comparing with aquatic ecosystems, soil systems, regardless of the high importance and complexity, have been less studied under widely existing and increasing MP contamination. This review, combined with data assimilation and meta-analysis methods, has summarized current contamination conditions of soil MPs across different sites reported in earlier studies. While performing this meta-analysis, we investigated the effects of MPs on soil biota including their numbers, biomass, diversity, and physiological properties. The results showed that abundance of soil MPs ranged from 0.34 to 410958.9 items kg-1 and concentration ranged from 0.002 to 67500 mg kg-1 across sites, with agricultural soils containing significantly lower abundance and concentration of MPs than others. Presence of MPs significantly decreased the individual number of soil biota, operational taxonomic unit, diversity index (Simpson), movement index and reproduction rate, whereas the mortality rate was significantly increased by the soil MPs. Despite these significant effects, MPs did not significantly alter the biomass of soil biota, which could be due to a counteraction of their negative and positive effects on different groups of soil organisms. Moreover, we observed that soil MPs could significantly increase the Chao1 index, suggesting that MPs may act as a food resource for the soil rare biosphere. Based on the existing knowledge, we suggest that future studies should focus on research areas that include but are not limited to methodological improvements, intensive field investigations, risk assessment from the perspective of soil food web and bioaccumulation, MPs induced antibiotic resistance, and restoration strategies to reduce their concentrations in soil.
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Soil microbial community drives the terrestrial carbon (C) cycling by C sources metabolism (i.e., organic C decomposition), however, the microbial response to changing acid rain frequency remains less studied, thus hampering global warming projection. Here, we manipulated a simulated experiment to decipher the impact of acid rain frequency (0, 30%, and 100%) on microbial community and C sources metabolism in the agricultural and forest soils of southern China, based on the phospholipid fatty acids (PLFAs) analysis and BIOLOG method, respectively. We found that changing acid rain frequency did not affect the microbial biomass and community structure of agricultural soil during the whole experiment period, while the 30% and 100% acid rain frequencies significantly decreased the microbial biomass, and altered the microbial community structure of forest soil at the early stage. However, changing acid rain frequency did not influence the microbial C sources metabolism in the agricultural soil, but 30% acid rain frequency significantly reduced the microbial utilization of carboxylic acids in the forest soil. Moreover, increasing acid rain frequency promoted the microbial community dissimilarities of forest soil. The microbial community structure and C sources utilization of agricultural soil were significantly related to soil available phosphorus content, while that of forest soil correlated with the soil available potassium content and temperature. Changes in soil environmental condition, soil acidification parameters and soil nutrients explained most of the variance of microbial community and C sources utilization (81% and 57%, respectively) in the forest soil, whereas great uncertainties of microbial community and C sources utilization existed in the agricultural soil with the explanatory proportion being 20% and 10%, respectively. Our findings suggest that the microbial community of forest soil is more sensitive to changing acid rain frequency than that of agricultural soil in a short term. These results support the prediction of microbes-driven C cycling dynamics in specific soil ecosystems in the context of changing acid rain frequency.