NL Treatment Research Articles

Dupilumab-associated (hyper)eosinophilia in patients with atopic dermatitis: a single-center cohort study of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

This study investigated the incidence and progression of (hyper)eosinophilia in patients with atopic dermatitis (AD) treated with dupilumab, using data from the TREAT NL registry cohort. In total, 38.5% of patients had (hyper)eosinophilia at baseline and/or during dupilumab treatment. (Hyper)eosinophilia was present at baseline in 43 (55.8%) patients and developed in 34 (44.2%) patients during treatment. Eosinophilia was transient, peaking at 6 months and normalizing by 18–24 months. One patient discontinued dupilumab due to persistent hypereosinophilia, but generally, eosinophilia did not affect treatment outcomes. In conclusion, dupilumab is found viable for patients with AD regardless of baseline eosinophilia, with temporary increases in eosinophil counts that are often not clinically significant.

Ascorbic Acid Improves Tomato Salt Tolerance by Regulating Ion Homeostasis and Proline Synthesis.

In this study, processing tomato (Solanum lycopersicum L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.

Resistance of consolidated lime mortars to freeze–thaw and salt crystallization cycles by different accelerated durability tests

The present study aimed at evaluating the performance of untreated and consolidated lime mortars, in terms of durability and possible “delayed incompatibility” of the consolidants. Lime mortars samples were treated by an aqueous solution of diammonium hydrogen phosphate (DAP treatment) and a dispersion of nanolimes (NL treatment). The samples were then subjected to accelerated ageing by different methods: (1) freeze–thaw cycles; (2) salt crystallization cycles based on the European standard EN 12370 (often considered as highly aggressive); (3) salt crystallization cycles according to a new recommendation proposed by the RILEM TC 271-ASC (designed to provide less aggressive and more reliable ageing). The results of the study showed that the DAP-based treatment was able to significantly reduce damage caused by freeze–thaw cycles and salt weathering cycles by the RILEM procedure. In the case of salt weathering by the EN procedure, some risk of “delayed incompatibility” was highlighted for DAP, which can be considered an outcome of the combination between the salt weathering procedure itself and the consolidating treatment. For both freeze–thaw and salt weathering by either procedure, the residual mechanical properties of DAP samples at the end of the cycles were significantly higher than those of the untreated references and of the NL samples, for which the effects of the NL treatment were very modest.

Real-world reported adverse events related to systemic immunomodulating therapy in patients with atopic dermatitis: Results from the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

Evidence on the (long-term) safety of systemic immunomodulating therapies in atopic dermatitis (AD) generated by real-world data is sparse. To describe real-world reported adverse drug reactions (AEs) related to systemic immunomodulating therapy in patients with AD and to compare the incidence rates of AEs with the Summaries of Product Characteristics (SmPCs). We conducted an observational prospective multi-centre cohort study, using the TREAT NL registry. All severe AEs, AEs of special interest and serious AEs in adult and paediatric patients on systemic immunomodulating treatment (ciclosporin, methotrexate, azathioprine, mycophenolic acid, dupilumab, tralokinumab, baricitinib and upadacitinib) were assessed. Incidences rates of all (potentially) drug-related AEs were standardized in patient years and compared to the cumulative incidences in the associated SmPCs. We collected 422 patient years of safety data from 266 patients, of whom 129 (48.5%) reported a total of 224 (potentially) drug-related AEs. Compared to dupilumab's SmPC, higher incidence rates were found for four AEs (reported ≥5 times): eosinophilia, blepharitis, dry eyes and head and neck erythema (i.e. dupilumab facial redness). A higher incidence rate of fatigue was found in patients on oral methotrexate in our cohort compared to the SmPC. Two new drug-related AEs (reported ≥5 times) were found in patients on dupilumab, including non-infectious conjunctivitis and meibomian gland dysfunction. Real-world reported AEs captured in AD patient registries can add information on the estimated incidence of AEs and benefit clinical decision aids. Future studies using data derived from the TREAT NL registry combined with data from other registries within the TREAT Registry Taskforce will provide more information on (rare) AEs associated with immunomodulating therapy in AD patients.

Effects of litter and root inputs on soil CH4 uptake rates and associated microbial abundances in natural temperature subalpine forests

Climate change altered the quantities of aboveground plant litter and root inputs, but the effects on soil CH4 uptake rates and underlying mechanisms remain unclear. To investigate these factors, a three-year detritus input and removal treatment (DIRT) study including six treatments (namely, CK, control; NL, litter removal; DL, double litter; NR, root exclusion; NRNL, root exclusion plus litter removal; and NRDL, root exclusion plus double litter) was conducted in broadleaf and coniferous forest subalpine forest ecosystems. The results showed that both the subalpine forest soils acted as sink for atmospheric CH4 across all treatments, while the broadleaf forest had consistently higher CH4 uptake rates than the coniferous forest. Based on the annual mean values, root exclusion (NR, NRNL and NRDL) significantly decreased soil CH4 uptake rates by 35.9 %, 31.0 % and 43.4 % in the broadleaf forest and 36.7 %, 31.9 % and 40.6 % in the coniferous forest compared with CK treatments, respectively. Meanwhile, the mean soil CH4 uptake rates were significantly reduced by 23.6 % and 17.3 % in the broadleaf forest and the coniferous forest under the DL treatments, respectively; nevertheless, the NL treatment significantly increased soil CH4 uptake rates by 19.68 % and 14.4 %, respectively. The results clearly demonstrated that root exclusion exerted a greater influence on soil CH4 uptake rates than plant litter manipulations. Correlation and redundancy analysis (RDA) revealed that the separation of root exclusion treatments from aboveground plant litter manipulations was based on higher soil water content, NH4+-N and NO3−-N concentrations, and lower DOC (dissolved organic carbon) concentrations and methanotroph pmoA gene abundance. The results suggest that future alterations in aboveground plant litter and root input, particularly a reduction in root input, can exert a stronger influence on regulating soil CH4 uptake than aboveground litter manipulations in subalpine forests with cold and humid climatic conditions in response to future climate scenarios.

Effects of Drip Tape Layout and Flow Rate on Water and Nitrogen Distributions within the Root Zone and Summer Maize Yield in Sandy Tidal Soil

Drip tape layout and flow rate are crucial variables that impact the effects of drip fertigation. To investigate the influence of drip tape layout and flow rate on the soil water and nitrogen transport in summer maize in sandy tidal soil, field experiments were conducted for two years. Two drip tape layouts were set: one tape serving for two crop rows (N) and one tape serving for each crop row (E), with two levels of drip flow rate, i.e., high (2 L/h; H) and low (1.3 L/h; L). The results show that under the same drip tape layout, the lower the drip emitter flow rate, the more upright the shape of wetted soil volume. The maximum vertical and horizontal water transport distance under NL treatment was higher than that under NH, EH, and EL treatments. After surface drip fertigation, nitrate nitrogen accumulated near and at the edge of the wetted soil volume. In 2020, under NL treatment, nitrate nitrogen transported to a 55 cm soil layer, which was 22.22%, 71.42%, and 57.14% deeper than that under NH, EH, and EL treatments, respectively. In 2021, nitrate nitrogen could transport to a 60 cm soil layer in both NL and NH treatments. The maximum concentration of ammonium nitrogen was nearby the emitter. Under NL treatment, ammonium nitrogen was transported to 48 and 60 cm soil layers below the emitter in 2020 and 2021, respectively, which was deeper than that observed under NH, EH, and EL treatments. The soil inorganic nitrogen residue of the NL was lower than that of the NH, EH, and EL treatments. Compared with NH, EH, and EL treatments, the two-year maize yield under NL treatment increased by 11.09%, 13.47%, and 8.66% on average, respectively. NL treatment exhibited the highest water use efficiency and nitrogen fertilizer productivity. Therefore, NL treatment (one drip tape serving for two rows with 1.3 L/h flow rate) could promote the absorption of water and nutrients, reduce inorganic nitrogen residue, and to obtain high maize yield in sandy tidal soil.

Soil enzyme activities responded differently to short-term litter input manipulation under coniferous and broad-leaved forests in the subalpine area of Southwest China

Litter plays an irreplaceable role in terrestrial ecosystem carbon (C), nitrogen (N) and phosphorus (P) cycling, and its decomposition is largely regulated by litter quality, soil properties and enzyme activities. However, how soil enzyme activities respond to change in litter input under different forest types remains unsolved. Here, we investigated soil enzyme activities involved in C (β-glucosidase, BG), N (N-acetyl-β-glucosaminidase, NAG; leucine aminopeptidase, LAP) and P (acid phosphatase, ACP) under short-term litter manipulations (i.e. Detritus Input and Removal Treatment-DIRT: control, CK; double litter, DL; no roots and double litter, NRDL; no litter, NL; no roots, NR; no roots and no litter, NRNL) and associated influencing drivers in a coniferous forest (Pinus yunnanensis) and a broad-leaved forest (Quercus pannosa) in the subalpine area of Southwest China. Our results showed that litter removal treatment significantly reduced enzyme activities under two forest soils, with the stronger effect of the NR treatment on decreased enzyme activities compared to the NL treatment, possibly because roots could provide more available C sources and nutrient to microorganism and also immediately interact with soil minerals. In contrast, the short-term litter addition did not significantly affect enzyme activities under both two forest soils. Additionally, the BG activities in coniferous forest soil were characterized by a lower effect size compared to those in broad-leaved forest soil under the litter removal (NL and NRNL) treatments, but the higher effect size of LAP and ACP activities were observed under the NRNL treatment in the coniferous forest soil. This finding was attributed to higher organic C sources in the coniferous forest soil which could promote other nutrients utilization by microorganisms, leading to more N and P enzyme productions. We observed that the enzyme activities in the coniferous forest soil were closely related to soil N, P contents and microbial traits (i.e., fungal and bacterial structure), while enzyme activities in the broad-leaved forest soil primarily depended on microclimates (soil temperature and moisture) and soil properties (pH, dissolved organic C and P contents) under short-term litter manipulations. Overall, our results revealed the different pattern and the regulatory mechanism of soil enzyme activities under litter input manipulation of two forests, thereby advancing understanding of soil enzyme dynamics in association with initial litter quality and soil properties under future global change.

Effects of LED Lighting Technology on Morphology, Antioxidant activity, and the Bioactive Compounds Accumulation of Anoectochilus burmannicus in the Greenhouse System

Anoectochilus burmannicus is valued for medicinal and ornamental purposes. It is characterized by beautiful foliage with attractively red-purple with bronze-colored veins blotches. Kinsenoside is an active compound in A. burmannicus which provided anti-inflammation properties, anti-obesity, and anti-diabetes properties. This study aimed to investigate the effects of light-emitting diode (LED) light quality on growth, photosynthetic pigment content, antioxidant activities, and the accumulation of bioactive compounds (polysaccharides, phenolics, and flavonoids) in A. burmannicus. Plants of A. burmannicus were grown under 6 different LED lighting in the greenhouse system for 60 days. The 6 treatments were blue light (BL, 24 h), cool light (CL, 24 h), natural light (NL, 12 h), red:blue 1:1 light (RBL, 24 h), red light (RL, 24 h), and warm light (WL, 24 h). The results showed that A. burmannicus plants have a positive effect on the growth and bioactive compounds under LED lights (24 h) technology compared to natural light (12 h). The WL treatment had the most positive effect on morphological parameters, while the BL treatment showed an enhancement in fresh weight and dry weight. NL treatment is increased the Chlorophyll a and Chlorophyll b content. The Carotenoid content increased in the RBL treatment phenolics content was considered tent were considered to be superior to the BL treatment. The total flavonoid content is increased in the RL and RBL treatments. The antioxidant activity of ABTS was significantly higher in the RBL treatment. This indicates that BL is required for the normal growth, biomass, and accumulation of polysaccharides and phenolic of A. burmannicus, while RBL is enhanced the accumulation of flavonoids and antioxidant activity. This technology is conducive to achieving large-scale sustainable production of high-quality medicinal plant materials. GRAPHICAL ABSTRACT

Tree roots exert greater influence on soil microbial necromass carbon than above-ground litter in subtropical natural and plantation forests

The stabilization of soil organic carbon (SOC) relies heavily on both the production of microbial necromass carbon (MNC) and its protection by clay minerals. Above- and below-ground carbon (C) sources differ not only in the C quality and quantity that drive MNC production but also in MNC-mineral interactions. Here we test the hypothesis that root litter and exudates play a more important role in the formation and stabilization of soil MNC than above-ground litterfall in a natural subtropical moist forest and a tree (Castanopsis carlesii) plantation of southeastern China. We employed a two-factorial design of field experiment consisting of four treatments: control (CT), litterfall exclusion (NL), root exclusion (NR), and no C input (NI). We found that NR treatment substantially reduced total soil MNC and both bacterial (BNC) and fungal (FNC) necromass C as well as fractions of MNC and FNC to total SOC in both natural and plantation forests, but did not alter ratios of FNC to BNC or BNC to total SOC. In comparison, NL treatment had no effect on the ratios of MNC, FNC or BNC to total SOC in both forests. Furthermore, NR treatment reduced both bacterial and fungal biomass, but NL treatment had no significant effect on bacterial or fungal biomass in the natural forests. Whereas the NR and NI treatments significantly reduced MNC and FNC in both forests, the NL treatment reduced MNC and FNC only in the natural forest and reduced BNC only in the plantation forest. Analysis of structural equation model revealed that the C treatments could alter the accumulation of MNC directly or indirectly through changing soil available substrates (i.e., DOC, NH4+) and microbial community structure. Our data suggests that plant roots exert a stronger influence on the production and stabilization of MNC than above-ground C source.

Two-year efficacy, safety, and drug survival of dupilumab for atopic dermatitis: A real-world Canadian multicenter retrospective study

To the Editor: Limited studies are available on the long-term efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis (AD) beyond the 52-week follow-up. A recent publication by our group showed favorable efficacy outcomes with no new safety signals in patients with AD over 52-weeks of dupilumab treatment.1 An observational prospective cohort study of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry showed consistent safety and efficacy outcomes up to week 84.

Increased Litter Greatly Enhancing Soil Respiration in Betula platyphylla Forests of Permafrost Region, Northeast China

The change of litter input can affect soil respiration (Rs) by influencing the availability of soil organic carbon and nutrients, regulating soil microenvironments, thus resulting in a profound influence on soil carbon cycle of the forest ecosystem. We conducted an aboveground litterfall manipulation experiment in different-aged Betula platyphylla forests (25-, 40- and 61-year-old) of the permafrost region, located in the northeast of China, during May to October in 2018, with each stand treated with doubling litter (litter addition, DL), litter exclusion (no-litter, NL) and control litter (CK). Our results indicated that Rs decreased under NL treatment compared with CK treatment. The effect size lessened with the increase in the stand age; the greatest reduction was found for young Betula platyphylla forest (24.46% for 25-year-old stand) and tended to stabilize with the growth of forest with the reduction of 15.65% and 15.23% for 40-and 61- year-old stands, respectively. Meanwhile, under DL treatment, Rs increased by 27.38%, 23.83% and 23.58% on 25-, 40- and 61-year-old stands, respectively. Our results also showed that the increase caused by DL treatment was larger than the reduction caused by NL treatment, leading to a priming effect, especially on 40- and 61-year-old stands. The change in litter input was the principal factor affecting the change of Rs under litter manipulation. The soil temperature was also a main factor affecting the contribution rate of litter to Rs of different-aged stands, which had a significant positive exponential correlation with Rs. This suggests that there is a significant relationship between litter and Rs, which consequently influences the soil carbon cycle in Betula platyphylla forests of the permafrost region, Northeast China. Our finding indicated the increased litter enhanced the Rs in Betula platyphylla forest, which may consequently increase the carbon emission in a warming climate in the future. It is of great importance for future forest management in the permafrost region, Northeast China.

Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: Results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry

Evidence on long-term dupilumab treatment for atopic dermatitis in daily practice is lacking. To investigate patient characteristics, treatment aspects, effectiveness, and safety of up to 84weeks of dupilumab treatment. An observational prospective cohort study was conducted of patients with atopic dermatitis starting dupilumab in routine clinical care. Of the 221 included patients, 103 used systemic therapy at baseline. At 84weeks, we found a change of -15.2 (SE, 1.7) for the Eczema Area and Severity Index, -16.9 (SE, 1.4) for the Patient-Oriented Eczema Measure, and -17.2 (SE, 1.6) for the Dermatology Life Quality Index. We found a trend for improvement over time for the Investigator Global Assessment and Numerical Rating Scale for pruritus. Severe (n=79) including serious (n=11) adverse events were observed in 69 patients. Eye complaints were most frequently reported (n=46). Twenty-one patients adjusted the regular dosing schedule, and 14 patients discontinued treatment, mainly due to ineffectiveness (n=7). Only adverse events of severe and serious nature were registered for feasibility reasons. Daily practice dupilumab treatment of up to 84weeks is generally well-tolerated, apart from the reporting of eye complaints. It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms, and quality of life.

Microbial regulation of soil carbon properties under nitrogen addition and plant inputs removal.

BackgroundSoil microbial communities and their associated enzyme activities play key roles in carbon cycling in terrestrial ecosystems. Soil microbial communities are sensitive to resource availability, but the mechanisms of microbial regulation have not been thoroughly investigated. Here, we tested the mechanistic relationships between microbial responses and multiple interacting resources.MethodsWe examined soil carbon properties, soil microbial community structure and carbon-related functions under nitrogen addition and plant inputs removal (litter removal (NL), root trench and litter removal (NRL)) in a pure Larix principis-rupprechtii plantation in northern China.ResultsWe found that nitrogen addition affected the soil microbial community structure, and that microbial biomass increased significantly once 100 kg ha−1 a−1 of nitrogen was added. The interactions between nitrogen addition and plant inputs removal significantly affected soil bacteria and their enzymatic activities (oxidases). The NL treatment enhanced soil microbial biomass under nitrogen addition. We also found that the biomass of gram-negative bacteria and saprotrophic fungi directly affected the soil microbial functions related to carbon turnover. The biomass of gram-negative bacteria and peroxidase activity were key factors controlling soil carbon dynamics. The interactions between nitrogen addition and plant inputs removal strengthened the correlation between the hydrolases and soil carbon.ConclusionsThis study showed that nitrogen addition and plant inputs removal could alter soil enzyme activities and further affect soil carbon turnover via microbial regulation. The increase in soil microbial biomass and the microbial regulation of soil carbon both need to be considered when developing effective sustainable forest management practices for northern China. Moreover, further studies are also needed to exactly understand how the complex interaction between the plant and below-ground processes affects the soil microbial community structure.

三工河流域琵琶柴群落凋落物对土壤有机碳固定的影响

PDF HTML阅读 XML下载 导出引用 引用提醒 三工河流域琵琶柴群落凋落物对土壤有机碳固定的影响 DOI: 10.5846/stxb201806301443 作者: 作者单位: 贵州大学动物科学学院,中国科学院植物研究所,贵州大学动物科学学院,贵州大学动物科学学院,贵州省草地技术试验推广站,贵州大学动物科学学院,贵州大学 作者简介: 通讯作者: 中图分类号: 基金项目: 贵州省科技厅-贵州大学联合基金项目（黔科合LH字[2017]7288号）；国家自然科学基金青年项目（31700390） Effects of litter on soil organic carbon fixation in Reaumuria soongorica communities in the Sangong River basin Author: Affiliation: College of Animal Science, Guizhou University,,,,,,College of Animal Science, Guizhou University Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:土壤有机碳是土壤碳库的重要组成部分，对生态系统生产力和全球碳循环有着重要作用。采用凋落物收集器和DIRT法（添加和去除凋落物法）研究三工河流域两处不同琵琶柴群落凋落物的产量、现存量、凋落物处理对土壤有机碳的影响。结果表明：群落1和群落2的凋落物产量季节变化趋势相同，均呈"N "型变化，在10月份达到最大值，7月或8月份达到次大值。凋落物现存量随季节均呈现" W"型变化，在10月份达到最大值，最大值分别为30.65 g/m2和57.87 g/m2。土壤有机碳随土壤深度的增加均逐渐降低，群落1和群落2分别下降了61.73%-62.39%和18.24%-25.84%。与对照处理相比，去除凋落物处理（NL）的群落1和群落2土壤有机碳分别降低了6.97%和18.38%；添加凋落物处理（DL）的土壤有机碳分别增加了19.64%和13.66%；去除凋落物处理（NL）的群落1和群落2土壤有机碳储量分别为1007.36 kg/hm2和709.30 kg/hm2，添加凋落物处理（DL）的土壤有机碳储量分别为1197.88 kg/hm2和1010.78 kg/hm2。双因素方差分析表明群落1的土层深度和三种处理对土壤有机碳的交互作用不显著，群落2的交互作用显著。回归分析显示：土壤水分、电导率、pH、容重和温度是导致两琵琶柴群落土壤有机碳不同的主要生态因子。相对较高的土壤pH和盐分含量抑制了凋落物的分解，导致凋落物现存量较高、土壤有机碳含量低；相对较高的土壤含水量和较小的容重，有利于土壤生物的活性和土壤有机碳的矿化，导致土壤有机碳含量降低。 Abstract:Soil organic carbon is an important component of the soil carbon pool,and plays a key role in ecosystem productivity and the global carbon cycle. In this research,litter removal and detritus input treatment (DIRT) methods were used to study the litter productivity,litter amount,and effects of different litter treatments on the soil organic carbon in two Reaumuria soongarica communities in the Sangong River Basin. The results showed that the litter productivities of two communities had almost identical seasonal changes;they reached their second-maximum and maximum values in July (August) and October,and both showed "N" distributions. The litter amount also presented similar seasonal change trends;both showed "W" distributions,and reached their maximum values of 30.65 g/m2 and 57.87 g/m2 in October,respectively. The soil organic carbon content gradually reduced with soil depth;Community 1 and Community 2 decreased by 61.73%-62.39% and 18.24%-25.84%,respectively. The average soil organic carbon content of Community 1 and Community 2 was reduced by 6.97% and 18.38% by the litter removal treatment (no litter,NL),and increased by 19.64% and 13.66% by the litter treatment (double litter,DL),respectively. The soil organic carbon storage values of Community 1 and Community 2 were 1007.36 kg/hm2 and 709.30 kg/hm2 after NL treatment,and 1197.88 kg/hm2 and 1010.78 kg/hm2 after DL treatment,respectively. Two-way analysis of variance showed that the interaction of soil organic carbon between the soil depths and three litter treatments was significant in Community 2,but not Community 1. Regression analysis showed that soil properties were determinants of the differences in soil organic carbon between the two communities. The relatively high litter amount and low soil organic carbon content were attributed to the high soil pH and salt content, which inhibited litter decomposition. Otherwise,the relatively high soil water content and low soil bulk density promoted both soil organism activity and soil organic carbon mineralization,which led to the decrease in soil organic carbon content. 参考文献 相似文献 引证文献

Synergistic Dual Inhibition of BCR-ABL1 and the Unfolded Protein Response Causes p38 MAPK-Mediated Cell Death and Sensitizes BCR-ABL1+ Acute Lymphoblastic Leukemia to Dexamethasone

Abstract Introduction The IRE1-XBP1 branch of Unfolded Protein Response (UPR) was previously shown to be pivotal for the survival of BCR-ABL1+ Acute Lymphoblastic Leukemia (ALL) cells. In this study, we identified a link between the IRE1 and BCR-ABL1 pathways which we harnessed for the pre-clinical application of a novel IRE1 inhibitor, MKC-8866, in combination with Nilotinib. The underlying mechanism was investigated by analysis of the phosphoproteome of BCR-ABL1+ ALL cell lines SUP-B15 and TOM-1. Upon dual treatment, the main force driving the cells toward death was ascribed to the activation of p38 MAPK. Additionally, the set of proteins affected under dual therapy suggested a possible regulation of glucorticoid receptor (GR) signaling that could modify the response to dexamethasone. Methods and Results SUP-B15 and TOM-1 cell lines were treated with vehicle, MKC-8866 (MKC, 30 µM) and nilotinib (NL, 0.5 µM) as single agents or in combination. Viability assays were performed in order to verify the synergistic effect of the treatment administered, evaluated using the Bliss formula. The combination of NL with MKC showed a striking synergism in both SUP-B15 and TOM-1 (Bliss calculation. Assumed additive effects: SUP-B15 24.2±20.6%, TOM-1 40.9±18.4% versus experimental values: SUP-B15 68.7±12.7%, TOM-1 78.8±4.9%). To validate the effect on a genetic level, pre-B cell derived from conditional Xbp1+/fl mice were transduced with BCR-ABL1and with either inducible cre or empty vector. The ALL-like cells were then treated with NL 0.5 µM and/or 4-hydroxytamoxifen (4OHT) 1µM to induce deletion. In agreement with the synergistic effect observed with the human cell lines, NL was shown to be significantly more effective in the presence of heterozygous deletion of Xbp1 (viable cells after 24 hours. NL: 65.2±0.3%, 4OHT + NL: 6.87±1.2%). To unravel the basis of this synergism, we performed a phosphoproteomic analysis of the two human cell lines treated for 16 hours with vehicle, MKC, NL and dual treatment, respectively. For this analysis, SUP-B15 and TOM-1 were lysed in 8M urea and digested using LysC/trypsin. The obtained peptides were labeled using the dimethyl isotope labeling method. Phosphopeptides were enriched using TiO2 beads and analyzed by nanoLC-MS/MS (Orbitrap Elite). The raw data were analyzed using MaxQuant and the Andromeda search engine against the human Uniprot database. The resulting information was further interpreted using the Perseus software package as well as the String and PhosphoPath apps in Cytoscape. The analysis of the regulated phosphorylated proteins highlighted a p38 MAPK differential regulation, with MKC alone or in combination causing its activation, and, in contrast, NL causing inhibition. Western Blot analyses investigating the activation of p38 MAPK showed increased phosphorylation of its main downstream target, heat shock protein beta-1 (HSPB1), in the presence of MKC alone or together with NL. Pharmacological inhibition of p38 MAPK activity by adding p38 MAPK inhibitor BIRB-796 (BIRB, 10µM) was able to rescue the cells from the concerted action induced by MKC and NL. Furthermore, the phosphoproteome pattern observed in the cells upon dual treatment suggested a regulation of crucial GR interactors. Therefore, we tested whether the studied combination would render the cells more responsive to the GR agonist dexamethasone (DEXA, 10 mg/L), cornerstone in ALL therapy. The viability assay revealed a striking enhancement of its cytotoxic effect. However, most of the effect was conveyed by the action of DEXA together with NL, with MKC adding only a small and non-significant accessory effect (percentages of viable cells compared to DMSO values after 24 hours treatment. SUP-B15: DEXA 83.9±4.2%; MKC + DEXA 81.6±5.1%; NL + DEXA 66.7±7.1% and MKC + NL + DEXA 59.8±7.3%. TOM-1: DEXA 78.2±8.4%; MKC + DEXA 74.1±5.1%; NL + DEXA 45.3±10.1% and MKC + NL + DEXA 45.2±8.1%). Conclusion By studying the phosphoproteome in BCR-ABL1+ ALL, we identified a possible underlying mechanism explaining the success of the combined action of NL and MKC-8866. The p38 MAPK axis was found responsible for the observed cytotoxic effect, elucidating important aspects of BCR-ABL1+ ALL biology. Overall, the successful treatment regime with NL and MKC in vitro, and its positive interaction with DEXA, provide a promising basis for further pre-clinical evaluation. Disclosures Patterson: Fosun Orinove PharmaTech, Inc.: Employment. Samali:Cell Stress Discoveries Ltd.: Other: co-founder, director and share holder . Brümmendorf:Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Merck: Consultancy; Novartis: Consultancy, Research Funding; Takeda: Consultancy. Appelmann:Novartis: Research Funding. Kharabi Masouleh:Janssen Research & Development: Employment.

Effects of detritus removal on soil carbon, nitrogen and phosphorus stoichiometry and related factors in a temperate deciduous forest in the Maoershan Mountain, China.

A detritus-removal experiment was conducted in a temperate deciduous broad-leaved forest in 2007 at the Maoershan Ecological Station in Northeast China, including two treatments: Litterfall removal (NL), root removal (NR). Soil water content, bulk density and the concentrations of soil C, N and P were measured in 2016. The results showed that the C concentration at the surface soil layer (0-10 cm) was reduced by 15.6% and 10.7% for the NL and NR treatments, respectively, while the weighted-mean soil C concentration in 0-30 cm depth was reduced by 7.9% and 4.6%, respectively. The N concentration of the surface layer in the NL treatment decreased by 10.2%, whereas the surface-soil P concentration in the NR treatment increased by 6.6%, resulting in reduced C:P and N:P for both treatments. The standardized major axis regressions showed that the regression slopes between the C, N and P at each layer of 0-30 cm soil depth differed significantly among the treatments. The intercepts of the regressions between soil C concentration and bulk density or soil water content had significant differences among the treatments. The results suggested that detritus-removal caused a coordinated variation in soil C, N and P stoichiometry and physical properties. Therefore, we recommend taking the effect on soil ecological stoichiometry into account in future detritus-removal experiments.

Continuous light affects onset of puberty and associated changes in pituitary gonadotropin subunit transcript levels, and plasma estradiol-17β and testosterone levels in Atlantic cod (Gadus morhua L.) females

Abstract To gain more insight in photoperiod modulation of timing of puberty and its endocrine control in female Atlantic cod, ovarian development, plasma sex steroid profiles and mRNA transcript levels of the pituitary gonadotropin subunits fshb , lhb and gpa were monitored under four different photoperiod regimes over 16 months. Pre-pubertal cod were subjected to ambient (NL group) or continuous (LL group) light in light-proof seawater tanks from June in their second year of life. On December 21, half of the NL group were transferred to continuous light (NL–LL group), and half of the LL group was moved to ambient light (LL–NL group). The fish were maintained under these conditions until November the following year. All females in the NL group entered puberty at two years of age as indicated by increasing gonadosomatic index (GSI), oocyte diameter, pituitary fshb , lhb and gpa mRNA levels, as well as plasma testosterone (T) and estradiol-17β (E2) levels. The NL females had hyaline oocytes or spent ovaries indicative of spawning in January to April, and subsequently started a new wave of maturation by October. Low GSI, oocyte diameter, pituitary fshb , lhb and gpa mRNA levels, and low plasma E2 and T levels demonstrated arrested maturation in most females in the LL group during the normal spawning season, while some maturing fish were noted towards the end of the experiment. Compared to LL females, NL females showed elevated levels of T by July in the first year of the study, fshb by September, E2 by October, and lhb by December. This suggests that the LL arresting effect initially was mediated by reduced Fsh signaling and lowered plasma T levels during the period of previtellogenic growth in summer and early autumn, followed by low E2 levels and inhibition of onset of vitellogenesis in late autumn and early winter. LL–NL treatment delayed puberty onset and completion by 5 months, while NL–LL resulted in earlier completion of the spawning season compared with NL. The accelerating and delaying effects observed on puberty and spawning in the LL–NL and NL–LL groups, respectively, were paralleled by similar shifts of the seasonal profiles of fshb , lhb , gpa , E2 and T.

Consequences of phosphorus interactions with calcium, phytase, and cholecalciferol on zootechnical performance and mineral retention in broiler chickens

The objective was to determine the effect of calcium (Ca), total phosphorus (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia ash percentage, and Ca and P retention in broilers until slaughter age. Broilers were randomly assigned to 12 treatments, each with 6 replicates, comprising 3 diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given 2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and 0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were 0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL treatment obtained the lowest BW, whereas BW of the NN and LL groups were comparable. Cholecalciferol significantly affected the BW, with differences up to 2.6 and 1.2% for the starter and grower phases, respectively. The highest cholecalciferol effect was found in combination with the NN treatment. The percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced diet was replaced by the NN and LL balanced diets, respectively. P release from phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and cholecalciferol had significantly favorable effects on retention values but these effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both diets with the balanced Ca/Ptot ratio resulted in the best performance, highest tibia ash percentage and P release from phytate. A reduction of the Aviagen (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the various phases did not negatively affect performance, bone development, and improved Ca and Ptot retention. The effects of supplementing cholecalciferol and phytase were additive but not significant and no synergism between both was present.

Appropriate nitrogen supply could improve soil microbial and chemical characteristics with Sophora davidii seedlings cultivated in water stress conditions

A greenhouse experiment was conducted to investigate the changes of soil microbial activities and chemical properties under different water and nitrogen (N) supply conditions. A completely randomized design was subjected to three water regimes (80%, 40% and 20% water field capacity (FC)) and three N supply regimes (control, N0: 0 mg N kg−1 soil; low N supply, Nl: 92 mg N kg−1 soil; and high N supply, Nh: 184 mg N kg−1 soil) by potting with 2-month-old Sophora davidii seedlings. Water stress decreased the content of soil organic carbon (C), available N and phosphorus (P), the ratio of C/N, the ratio of C/P, as well as activities of soil invertase, urease and alkaline phosphatase, but not reduced microbial biomass C, N and P contents. Soil microbial and chemical characteristics also exhibited strong responses to N supply, and these responses were inconsistent among N supply levels. The contents of soil organic C and available P showed stronger positive responses to Nl than to Nh, while the available N content increased with increasing N supply. Additionally, Nl rather than the other two N treatments led to increased microbial biomass N and invertase activity under 20% FC treatment, even though the invertase activity increased in Nh treatment under 40% FC and 80% FC treatments. Nl treatment also increased the C/P ratio and alkaline phosphatase activity. These results suggest that water and N co-limited nutrient mineralization and microbial activity, and that these characteristics responded positively to Nl. Therefore, appropriate or low N supply is recommended to increase soil quality restrained by water stress, thereby facilitating S. davidii seedling establishment under water deficit conditions.

Evaluation of Stocking Density and Light Level on the Growth and Survival of the Pacific White Shrimp, Litopenaeus vannamei, Reared in Zero-Exchange Systems

The objective of this study was to evaluate the effects and interactions of stocking density and light level on the growth and survival of Litopenaeus vannamei in zero-exchange mixed biofloc systems. The necessity of light and its effects on stocking density could provide essential information for efficient system design in temperate regions. Twelve, 3800-L conical-bottom tanks housed in a greenhouse were filled with dechlorinated city water, adjusted to 25 ppt salinity, inoculated with mixed biofloc communities, and randomly assigned to one of four different treatment combinations. The study was a 2 × 2 factorial arrangement with main effects being stocking density (182 shrimp/m2 [low density; LD] vs. 364 shrimp/m2 [high density; HD]) and light (natural light [NL] vs. low level artificial [LL]) with three replicate tanks per treatment. Tanks in the NL treatment received ambient greenhouse light. For the LL treatment black plastic was used to block NL and a single 60-W incandescent bulb was hung over each low-light tank and operated on a 12:12 h schedule. Juvenile L. vannamei (0.40 ± 0.28 g) were stocked in rotation into each tank and fed a 35% protein diet twice daily at an initial 10% of body weight, gradually decreasing to 3% of body weight prior to harvest. After 12 wk, there was a statistically significant (P≤ 0.05) interaction between density and light level; therefore, data were analyzed in terms of treatment combinations. Average harvest weight of shrimp was significantly higher (P≤ 0.05) in the LD/NL treatment (14.5 g) than in the HD/LL treatment (12.4 g), but neither was significantly different from HD/NL (13.6 g) and LD/LL (13.4 g). Survival of shrimp was significantly lower (P≤ 0.05) in the HD/LL treatment (61.8%) than in the LD/NL (89.8%) and LD/LL (89.0%) treatments. Survival in the HD/NL treatment (82.7%) was intermediate and not significantly different (P > 0.05) from the other treatments. Harvest yield was significantly greater (P≤ 0.05) in the HD/NL treatment (4.1 kg/m2) than in the LD/NL, LD/LL, and HD/LL treatments (2.4, 2.2, and 2.8 kg/m2, respectively), which were not significantly different (P > 0.05) from each other. These data indicate that a combination of high stocking rate with high light levels or NL may be needed to achieve maximum production; however, relatively low levels of artificial light may be suitable at low stocking densities. Further research should investigate the type and amount of light needed to achieve optimal results.