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Background: Infantile epileptic spasms syndrome (IESS) is a serious disease in infants, and it usually evolves to other epilepsy types or syndromes, especially refractory or super-refractory focal epilepsies. Although adrenocorticotropic hormone (ACTH) is one of the first-line and effective treatment plans for IESS, it has serious side effects and is not sufficiently effective. Methods: A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate (MgSO4) therapy for IESS in two hospital centers was conducted. The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography (EEG). To reduce the confounding bias between the two groups, we used SPSS for the propensity score matching (PSM) analysis. Results: We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH alone. Only 1005 patients were enrolled in the treatment (ACTH combined with MgSO4: 744, ACTH: 261), and both treatment plans had a more than 55% response rate. However, compared to patients treated with ACTH alone, those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia EEG. After PSM, the two groups also showed significant differences in responder rate [70.8% (95% confidence interval, CI) = 66.7%–74.8%) vs. 53.8% (95% CI = 47.4%–60.2%), P < 0.001], seizure frequency (P < 0.001) and hypsarrhythmia EEG resolution (P < 0.001). Notably, multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome. Patients with less than 3 months of lead time responded to the treatment much better than those with > 3 months (P < 0.05). In addition, the overall incidence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group (31.4% vs. 63.1%, P < 0.001). During the treatment, only infection (P = 0.045) and hypertension (P = 0.025) were significantly different between the two groups, and no baby died. Conclusion: Our findings support that ACTH combined with MgSO4 is a more effective short-term treatment protocol for patients with IESS than ACTH alone, especially for those patients with short lead times to treatment. B8W4opQ6sCQLegVDyqUwmi Video Abstract (MP4 533623 KB) [ABSTRACT FROM AUTHOR]

Background: Renal angiomyolipoma (RAML) is the most common kidney lesion in patients with tuberous sclerosis complex (TSC), affecting about 80% of patients. It is a benign tumor that grows over time, usually bilaterally, and can easily lead to kidney complications such as acute hemorrhage. Herein, we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis. Methods: A prospective cohort study was conducted. Sirolimus was initiated at 1 mg/(m2 × day), and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5–10 ng/mL. The disappearance of RAML in children after sirolimus treatment was observed, and Cox regression was used to screen the factors affecting tumor disappearance. Results: One hundred and twenty-six patients who met the criteria were analyzed. After 3 months, 6 months, 12 months, and 24 months of follow-up, tumors disappeared in 18 (14.3%), 30 (23.8%), 39 (31.0%), and 42 (33.3%) children, respectively. Tumors disappeared in 50 (39.7%) children by the last visit of each individual, and 30 (60%) of them occurred within 6 months. The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate. Thirty-six (29%) patients had stomatitis during the entire treatment period, and no serious adverse reactions were observed. Conclusions: Sirolimus could promote the disappearance of TSC-related RAML. The disappearance rate was correlated with the maximum diameter at baseline, and the smaller the tumor was, the higher the disappearance rate. It is well tolerated in the treatment of RAML associated with TSC. -y3UuAfomqvu4rovYkw6j4 [ABSTRACT FROM AUTHOR]

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones. [ABSTRACT FROM AUTHOR]

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective : Previous studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine neurotransmitter-degrading enzyme involved in the degradation of norepinephrine, epinephrine and serotonin. To find a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan‒Meier (KM) plotter were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blotting analysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism of cancer cell glycolysis. MAOA expression and patient survival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples. Results: MAOA expression was significantly downregulated in gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with the SUXmax value of PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also reported that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients. Conclusions: MAOA attenuated glycolysis and inhibited the progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinical therapeutic regimens. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is a malignant tumour with high mortality, and liver metastasis is one of the main causes of poor prognosis. SLIT- and NTRK-like family member 4 (SLITRK4) plays an important role in the nervous system, such as synapse formation. Our study aimed to explore the functional role of SLITRK4 in GC and liver metastasis. Methods: The mRNA level of SLITRK4 was evaluated using publicly available transcriptome GEO datasets and Renji cohort. The protein level of SLITRK4 in the tissue microarray of GC was observed using immunohistochemistry. Cell Counting Kit-8, colony formation, transwell migration assays in vitro and mouse model of liver metastasis in vivo was performed to investigate the functional roles of SLITRK4 in GC. Bioinformatics predictions and Co-IP experiments were applied to screen and identify SLITRK4-binding proteins. Western blot was performed to detect Tyrosine Kinase receptor B (TrkB)-related signaling molecules. Results: By comparing primary and liver metastases from GC, SLITRK4 was found to be upregulated in tissues of GC with liver metastasis and to be closely related to poor clinical prognosis. SLITRK4 knockdown significantly abrogated the growth, invasion, and metastasis of GC in vitro and in vivo. Further study revealed that SLITRK4 could interact with Canopy FGF Signalling Regulator 3 (CNPY3), thus enhancing TrkB- related signaling by promoting the endocytosis and recycling of the TrkB receptor. Conclusion: In conclusion, the CNPY3-SLITRK4 axis contributes to liver metastasis of GC according to the TrkB-related signaling pathway. which may be a therapeutic target for the treatment of GC with liver metastasis. [ABSTRACT FROM AUTHOR]

This study explores how parametric uncertainties in the production affect failure tensile loads of reinforced thermoplastic pipes (RTPs) under combined loading conditions. The stress distributions in RTPs are examined with three-dimensional (3D) elasticity theory, and the analytical micromechanics of composites are evaluated. To evaluate the failure mechanisms for RTPs, 3D Hashin—Yeh failure criteria are combined with the damage evolution model to establish a progressive failure model. The theoretical model has been validated through numerical simulations and axial tensile tests data. To analyze how randomness of relevant parameters affects the first-ply failure (FPF) tensile load and final failure (FF) tensile load in RTPs, many samples are produced with the Monte—Carlo approach. The stochastic analysis results are statistically evaluated through the Weibull probability density distribution function. For the randomness of production parameters, the failure tensile load of RTPs fluctuates near the mean value. As the ply number at the reinforced layer increases, the dispersion of failure tensile load increases, with a high probability that the FPF tensile load of RTPs is lower than the mean value. [ABSTRACT FROM AUTHOR]

Purpose: There was no evidence whether the mammalian/mechanistic target of rapamycin pathway hyperactivation and long-term use of mTOR inhibitors have any effects on the physical development of children. The aim was to evaluate these effects by comparing the physical development of children with TSC and normal children. Methods: A total of 120 eligible children were enrolled. They were administered sirolimus and followed for at least 12 months. Height, weight, BMI and lipid metabolism index were collected during treatment. Pearson's chi-square and Fisher's exact test were used for comparison of proportions of patients exhibiting normal and abnormal physical growth before and after 1 year of treatment. Logistic regression was used to evaluate the influence of age, sex and abnormal lipid metabolism on the increased BMIs of TSC patients after treatment. Results: Most of the enrolled TSC children were in the normal height, weight and BMI ranges at baseline (91.7%, 95.8% and 78.3%, respectively). Most remained in the normal height, weight and BMI ranges after 1 year of sirolimus treatment (94.2%, 95% and 76.7%, respectively). There was no significant difference in the proportion of physical development before and after treatment (p > 0.05). Thirty-eight (38/106, 35.8%) patients had increased BMIs after 1 year of treatment, but there was no significant correlation between age, sex and lipid metabolism and increased BMI. Conclusions: Overactivation of the mTOR pathway and long-term administration of sirolimus does not affect the physical development of children with TSC. [ABSTRACT FROM AUTHOR]

This paper presents a study on the tensile properties of reinforced thermoplastic pipes (RTPs). A mechanical model of RTPs with an arbitrary number of reinforced layers under tensile action is constructed by combining the constitutive relationship of elastoplastic materials with the continuous displacement condition. On this basis, the effects of various parameters such as the winding angle, the number of structurally reinforced layers, and the inner polyethylene (PE) liner thickness on the tensile properties of the RTPs were analyzed, and a tensile test was carried out for validation. The results showed that the winding angle of the structurally reinforced layers was the main factor affecting an RTP's tensile performance—decreases in the winding angle significantly improved its tensile ability, especially the longitudinal strength. With ±45° as the demarcation point, the winding angle smaller than ±45° will result in higher strength in longitudinal direction, and the lifting effect on RTP's mechanical properties of the increasing number of reinforcement layers was better than that of the increasing thickness of the lining layer; when the winding angle was larger than ±45°, the opposite results were obtained. The fibre load was more sensitive to the winding angle than the PE load. [ABSTRACT FROM AUTHOR]

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Tree shrews, possessing higher developed motor function than rats, were more suitable to study neurological behavior after spinal cord injury (SCI). Here, we established a feasible behavioral assessment method to detect the degree of ethology recovery in tree shrew subjected to spinal cord transection (SCT). Tree shrews were divided into normal group, sham group, and SCT group. The tree shrew in sham group was subjected to laminectomy without SCI, while the tree shrews in the SCT group were subjected to a complete SCT in thoracic 10 (T10). A novel neurobehavior assessment scale was established, in which, the behavior index including slow advancement, fast advancement, standing, shaking head, voluntary jump, lateral movement, and tail status, was determined, respectively. Meanwhile, magnetic resonance imaging (MRI) was applied to observe the structure of the spinal cord, and diffusion tensor imaging (DTI)-based white matter mapping was used to show the fibers of the spinal cord. As a result, a marked decrease in locomotor function and consciousness was seen in tree shrews with SCT, and the detection of MRI showed the collapsing of nerve fibers after SCT is completely cut and there is corresponding to the behavior change. Together, the present study provided a novel and feasible method that can be used to assess the neurobehavior in SCT model from tree shrews, which may be useful to the SCI translational study in future preclinic trial. [ABSTRACT FROM AUTHOR]

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1−/−). Then, we characterized the survival rate and behavioral phenotype of CPLX1−/− rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1−/− rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1−/− rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1−/− rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1−/− rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1. [ABSTRACT FROM AUTHOR]

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia. [ABSTRACT FROM AUTHOR]

Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia (ACI), we established a middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor β (GMFB) based on quantitative analysis of the global rat serum proteome. Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was over-expressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation (OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium (CM) after OGD. We then used the CM to culture pulmonary microvascular endothelial cells (PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover, ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells. In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI. [ABSTRACT FROM AUTHOR]

CaCl2 encapsulated was placed in the hydrothermal reactor of an aqueous solution of Na2CO3 and dodecyl dimethyl benzyl ammonium bromide for synthesis of two samples of calcium carbonate by an improved hydrothermal method and one-pot method. Their crystal structure, morphology, chemical composition, and thermal stability of the synthesized samples of calcium carbonate were investigated by XRD, FTIR, SEM, EDS and TGDSC. The sterilization activity of the as-prepared samples was evaluated by killing of Sarcina lutea bacteria. The results indicated that the regular cube capsule-assisted calcium carbonate prepared by hydrothermal process was doped with dodecyl dimethyl benzyl ammonium bromide. Under the same condition, the spindle-shaped calcium carbonate synthesized the one-pot method was not doped with dodecyl dimethyl benzyl ammonium bromide. Among the samples of calcium carbonate, capsule-assisted calcium carbonate had shown better antibacterial effect for Sarcina lutea: in 48 h after its inhibition a zone diameter was 12.3 mm. [ABSTRACT FROM AUTHOR]

Most of the exist action recognition methods mainly utilize spatio-temporal descriptors of single interest point while ignoring their potential integral information, such as spatial distribution information. By combining local spatio-temporal feature and global positional distribution information (PDI) of interest points, a novel motion descriptor is proposed in this paper. The proposed method detects interest points by using an improved interest point detection method. Then, 3-dimensional scale-invariant feature transform (3D SIFT) descriptors are extracted for every interest point. In order to obtain a compact description and efficient computation, the principal component analysis (PCA) method is utilized twice on the 3D SIFT descriptors of single frame and multiple frames. Simultaneously, the PDI of the interest points are computed and combined with the above features. The combined features are quantified and selected and finally tested by using the support vector machine (SVM) recognition algorithm on the public KTH dataset. The testing results have showed that the recognition rate has been significantly improved and the proposed features can more accurately describe human motion with high adaptability to scenarios. [ABSTRACT FROM AUTHOR]

In order to improve the efficiency of bioleaching heavy metal from the contaminated soil using Penicillium chrysogenum ( P. chrysogenum), experiment was conducted to evaluate the influence of heavy metal stress on P. chrysogenum during bioleaching. The morphology and physiology of P. chrysogenum were observed. Assuming that the heavy metals are all leached out from the experiment soil, heavy metals are added into the agar medium by simulating the heavy metal content in the soil. It is concluded that the survivable heavy metal contaminated soil mass range for P. chrysogenum is 2.5-5.0 g. As for biomass determination, the contaminated soil is added into the liquid medium directly. The soil mass that P. chrysogenum can be survivable is in the range of 2.5-8.75 g. In this mass range, the biomass of P. chrysogenum is bigger than that of the control sample. 10 g soil mass is the threshold of the growth of P. chrysogenum. 102.2 mg/L gluconic acid, 156.4 mg/L oxalic acid, 191.6 mg/L pyruvic acid, 0.02 mg/L citric acid, 0.03 mg/L malic acid and 70.6 mg/L succinic acid are determined after 15 d bioleaching. The mycelium is broken into fragments, and heavy metals are adsorbed on the cell wall or transported into the cytoplasm during bioleaching. The GOD activity declines from 1.08 U/mL to 0.2 U/mL under 400 mg/L of multi-metal stress. The influence of Pb on GOD activity is bigger than that of Cr and Cd, and the GOD activity is not influenced apparently by Mn, Zn and Cu. [ABSTRACT FROM AUTHOR]

The aim of this study is increasing the connection strength between the asphalt course and the semi-rigid base course. A revolutionary method was put forward, which used nails to connect the asphalt course to the rigid or semi-rigid base course. The interlaminar shear and fatigue performance of asphalt pavement were evaluated through shear and fatigue testing by using nails to connect the asphalt course with the semi-rigid base course. The results show that shear strength of the interface connected by the nails between the asphalt mixture and the cement stabilized macadam was double that of the interface connected by the modified asphalt emulsion prime and seal coat. Its fatigue life was extended 47.3% compared with that of the interface linked by the modified asphalt emulsion prime and seal coat. We demonstrate that the performance of the interlayer connection and asphalt pavement structure integrity can be improved by incorporating nails to connect the asphalt course with the semi-rigid base course. [ABSTRACT FROM AUTHOR]

gram negative bacterium, named JDC-16, which can grow well on the substrate of phthalic acid esters (PAEs) as the sole source of carbon and energy, was isolated from river sludge. Based on the morphology, physiological and biochemical properties and analysis of 16S rRNA gene sequence, it was preliminarily identified belonging to the genus Acinetobacter. The result of substrates utilization range indicates that strain JDC-16 can utilize a variety of phthalates except for diisononyl phthalate (DINP). The degradation tests using diethyl phthalate (DEP) as the model compound show that the optimal pH and temperature for DEP degradation by Acinetobacter sp. JDC-16 is 8.0 and 35 °C, respectively. Meanwhile, degradation kinetics under various initial concentrations of DEP reveals that substrate depletion curves fit well with the modified Gompertz model with high correlation coefficient ( R>0.99). Furthermore, the substrate induction test indicates that DEP-induction can apparently shorten the lag phase and enhance the degradation rate. This work highlights the potential of this isolate for bioremediation of phthalates-contaminated environments. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s12031-020-01741-2 [ABSTRACT FROM AUTHOR]

Scientific management of nitrogen (N) fertilizer has a significant effect on yield while also reducing the environmental risks. In this study, we conducted field experiments over three years at two different sites (Zhengzhou and Shangshui) in Henan Province, China, using different N application rates (0, 90,180, 270, and 360 kg ha−1) to determine the relationships between soil N supply and N demand in winter wheat (Triticum aestivum L.). Optimal N input was then determined. Both sites showed the same trend. Namely, aboveground N uptake and soil nitrate N (NO3−-N) increased with increasing N, while NO3−-N decreased with increasing soil depth, gradually moving downwards with growth. A significant correlation (p < 0.001) between increasing aboveground N uptake and increasing NO3−-N was also observed under N application, with the best relationships occurring in the 20–60 cm layer during jointing-anthesis (R2 = 0.402–0.431) and the 20–80 cm layer at maturity (R2 = 0.474). Root weight density showed the same spatial-temporal characteristics as NO3−-N, following a unimodal trend with increasing N, and peaking at 90 kg ha−1. The root weight density was mainly distributed in the 0–60 cm layer (above 80%), with the 20–60 cm layer accounting for 30% of the total root system. In this layer, the root weight density was also significantly positively correlated with aboveground N uptake. Wheat yield reached saturation under high N (>270 kg ha−1), with a sharp decrease in N use efficiency (NUE) and linear increase in residual NO3−-N. To balance yield and the risk of environmental pollution in the experimental area, an N application rate of 180–270 kg ha−1 is recommended under sufficient irrigation, thereby supporting a well-developed root system while ensuring balance between N supply and demand. [ABSTRACT FROM AUTHOR]