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Improving the accuracy of anthropogenic volatile organic compounds (VOCs) emission inventory is crucial for reducing atmospheric pollution and formulating control policy of air pollution. In this study, an anthropogenic speciated VOCs emission inventory was established for Central China represented by Henan Province at a 3 km × 3 km spatial resolution based on the emission factor method. The 2019 VOCs emission in Henan Province was 1003.5 Gg, while industrial process source (33.7%) was the highest emission source, Zhengzhou (17.9%) was the city with highest emission and April and August were the months with the more emissions. High VOCs emission regions were concentrated in downtown areas and industrial parks. Alkanes and aromatic hydrocarbons were the main VOCs contribution groups. The species composition, source contribution and spatial distribution were verified and evaluated through tracer ratio method (TR), Positive Matrix Factorization Model (PMF) and remote sensing inversion (RSI). Results show that both the emission results by emission inventory (EI) (15.7 Gg) and by TR method (13.6 Gg) and source contribution by EI and PMF are familiar. The spatial distribution of HCHO primary emission based on RSI is basically consistent with that of HCHO emission based on EI with a R-value of 0.73. The verification results show that the VOCs emission inventory and speciated emission inventory established in this study are relatively reliable.

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The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

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An important aspect in groundwater remediation is to understand changes of multiphase fluid front morphology and stagnant regions on macro scale. However, the prediction of those changes during two-phase flow remains a challenging task due to the interplay of various physical factors. Recent laboratory experiments have demonstrated tracers' ability to predict deformation in the front of a two-phase flow system by utilizing a new reactive tracer known as, the kinetic interface sensitive tracer (KIS). This research employs a reactive transport model coupled with a macro-scale two-phase flow model to numerically analyse how viscosity ratio, capillary number, and heterogeneities on the tracer's signal and its impact the frontal deformation. One homogeneous and two heterogeneous types of porous media are considered. The background porous medium is a fine-grained, low-permeability medium, with a coarser, high-permeability lenses, generating heterogeneous material properties. The high-permeability lenses account for 25 % of the total model area and are arranged in either periodic or random patterns. The findings are evaluated using four parameters (effective front length, swept area, front roughness, and transition zone length). The flow patterns dominating the shape of the front are characterized by the viscous and capillary forces i.e. capillary number and the viscosity ratio between the two fluids. The results show that changes in flow regimes can be quantified using effective front length, thus employing the effective front length the viscous fingering regions can be quantified. Furthermore, front roughness and transition zone length are extracted and their relevance to the by-passed zones is presented. The slope of the reactive KIS tracer breakthrough curve, plotted on a phase diagram, can also be used to predict the existence of the by-passed zones for a low viscosity ratio. Finally, changes in front roughness and transition zone length induced by the inclusions are correlated to the slope of the KIS tracer BTC. The findings of this study can contribute to a better understanding of the impact of different flow regimes on the KIS tracer breakthrough signals and the linkages between the tracer signals and the front sizes.

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Bone is influenced by many factors such as genetics and mechanical loading, but the short-term physiological effects of these factors on bone (re)modelling are not well characterised. This study investigated the effects of endurance trainability phenotype, sex, and interval running training (7-week intervention) on bone collagen formation in rats using a deuterium oxide stable isotope tracer method. Bone samples of the femur diaphysis, proximal tibia, mid-shaft tibia, and distal tibia were collected after necropsy from forty-six 9 ±â€¯3-month male and female rats selectively bred for yielding low (LRT) or high (HRT) responses to endurance training. Bone collagen proteins were isolated and hydrolysed, and fractional synthetic rates (FSRs) were determined by the incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. There was a significant large main effect of phenotype at the femur site (p < 0.001; η2g = 0.473) with HRT rats showing greater bone collagen FSRs than LRT rats. There was a significant large main effect of phenotype (p = 0.008; η2g = 0.178) and a significant large main effect of sex (p = 0.005; η2g = 0.196) at the proximal site of the tibia with HRT rats showing greater bone collagen FSRs than LRT rats, and male rats showing greater bone collagen FSRs compared to female rats. There was a significant large main effect of training at the mid-shaft site of the tibia (p = 0.012; η2g = 0.159), with rats that underwent interval running training having greater bone collagen FSRs than control rats. Similarly, there was a significant large main effect of training at the distal site of the tibia (p = 0.050; η2g = 0.156), with rats in the interval running training group having greater bone collagen FSRs compared to rats in the control group. Collectively, this evidence highlights that bone responses to physiological effects are site-specific, indicating that interval running training has positive effects on bone collagen synthesis at the tibial mid-shaft and distal sites, whilst genetic factors affect bone collagen synthesis at the femur diaphysis (phenotype) and proximal tibia (phenotype and sex) in rats.

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Quantitative total-body PET imaging of blood flow can be performed with freely diffusible flow radiotracers such as 15O-water and 11C-butanol, but their short half-lives necessitate close access to a cyclotron. Past efforts to measure blood flow with the widely available radiotracer 18F-fluorodeoxyglucose (FDG) were limited to tissues with high 18F-FDG extraction fraction. In this study, we developed an early-dynamic 18F-FDG PET method with high temporal resolution kinetic modeling to assess total-body blood flow based on deriving the vascular transit time of 18F-FDG and conducted a pilot comparison study against a 11C-butanol reference. Methods: The first two minutes of dynamic PET scans were reconstructed at high temporal resolution (60×1 s, 30×2 s) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate ( K 1 ) as a surrogate of blood flow, our method directly estimates blood flow using a distributed kinetic model (adiabatic approximation to the tissue homogeneity model; AATH). To validate our 18F-FDG measurements of blood flow against a flow radiotracer, we analyzed total-body dynamic PET images of six human participants scanned with both 18F-FDG and 11C-butanol. An additional thirty-four total-body dynamic 18F-FDG PET scans of healthy participants were analyzed for comparison against literature blood flow ranges. Regional blood flow was estimated across the body and total-body parametric imaging of blood flow was conducted for visual assessment. AATH and standard compartment model fitting was compared by the Akaike Information Criterion at different temporal resolutions. Results: 18F-FDG blood flow was in quantitative agreement with flow measured from 11C-butanol across same-subject regional measurements (Pearson R=0.955, p<0.001; linear regression y=0.973x-0.012), which was visually corroborated by total-body blood flow parametric imaging. Our method resolved a wide range of blood flow values across the body in broad agreement with literature ranges (e.g., healthy cohort average: 0.51±0.12 ml/min/cm3 in the cerebral cortex and 2.03±0.64 ml/min/cm3 in the lungs, respectively). High temporal resolution (1 to 2 s) was critical to enabling AATH modeling over standard compartment modeling. Conclusions: Total-body blood flow imaging was feasible using early-dynamic 18F-FDG PET with high-temporal resolution kinetic modeling. Combined with standard 18F-FDG PET methods, this method may enable efficient single-tracer flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience.

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Nitrogen (N) fertilizer is often used in production practice to effectively maintain crop productivity; however, low nitrogen use efficiency (Nue) has always been a problem. Specifically, the transformation and utilization of nitrogen fertilizer by biochar and the driving mechanisms remain unclear. We used four biochar application rates (0, 3750, 7500, and 11,250 kg·ha-1) and analyzed the effects of biochar on nitrogen fertilizer utilization, residue, and loss over three years using 15N isotope tracer technology. The results showed that (1) biochar improved the nitrogen use efficiency of maize plants, reduced total nitrogen loss, and increased the maize yield. Compared to the control treatment in the same year, the application of 7500 kg·ha-1 biochar increased the nitrogen use efficiency by 24.27 %, 27.77 %, and 35.82 %, and the yield increased by 21.1 %, 26.7 %, and 24.5 %, respectively. (2) Biochar increased the proportion of mineral nitrogen supplied by fertilizer in the mineral nitrogen pool. The application of 7500 kg·ha-1 biochar increased mineral nitrogen by 3.05 %, 3.22 %, and 3.8 %, respectively, compared to the control treatments in the same year. Biochar promoted the transformation of nitrogen in the 0-40 cm soil layer to three different soil nitrogen pools, especially the organic nitrogen pool. (3) Biochar significantly improved the soil bacterial community and increased the abundances of N transformation functional genes. The redundancy analysis (RDA) showed that the gdhA mineralization gene was the driving factor of nitrogen fertilizer transformation, contributing 43.6 % of the variance. In summary, the application of 7500 kg·ha-1 of biochar for two consecutive years was conducive to maintaining farmland soil fertility, while its use would not be recommended for more than three consecutive years.

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The changing global climate brings a gradual yet constant and adverse shift in crop production. Grain crop plants, particularly cereals and legumes, respond varyingly to adverse climate, including reduction in grain yield and changes to their nutrient densities. An understanding of specific changes to crop systems under differing climatic conditions can help in planning diets to meet human nutrient sufficiency. Grain protein content is also affected by adverse environmental factors. Deficits in protein yield, linked to changes in grain or seed protein and antinutrient concentrations, have been reported in major food crops when exposed to elevated carbon dioxide, high temperature, drought, and humidity. These changes, in addition to affecting the quantity of indispensable or essential amino acids (IAA), also impact their bioavailability. Therefore, it is important to assess consequences of climate change on grain protein quality. An important tool to measure grain protein quality, is measuring its digestibility at the level of the ileum and its IAA concentration, linked to a metric called the Digestible IAA Score (DIAAS). A minimally invasive technique called the dual isotope tracer technique, which measures IAA digestibility after simultaneous administration of two different intrinsically labelled protein sources, one a test protein (2H/15N) and one a reference protein (13C) of predetermined digestibility, has been used in evaluation of grain protein IAA digestibility, and promises more in the evaluation of changes based on climate. This review discusses climate induced changes to grain protein quality through the prism of IAA digestibility, using the dual isotope tracer technique.

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The rapid expansion of coastal aquaculture has led to an increase in the coverage of aquaculture ponds, where intense feed-derived nitrogen is causing significant emissions of nitrous oxide (N2O). Multiple N2O production pathways and the relative importance of water column vs. sedimentary production in aquaculture ponds remain uncertain. Clarifying these pathways is vital for sustainable aquaculture development. Using 15N-labeled dissolved inorganic nitrogen, the pathways and rates of N2O production in subtropical aquaculture ponds located in south China, cultivating whiteleg shrimp, Japanese seabass, and giant river prawn, were successfully characterized. Total N2O production rates ranged from 6 to 70 µmol-N m-2 d-1, with the shrimp pond exhibiting the highest total N2O production rates, followed by ponds for seabass and prawn. These differences are primarily due to varying feed amounts causing differences in dissolved nutrients in water column and sediment. Particularly, nutrient and organic matter accumulation at the surface sediment stimulated N2O production. The oxygenated sediment on a centimeter scale could produce substantially more N2O compared to the water column above on a meter scale. Partial denitrification, i.e., nitrate and nitrite reduction to N2O, was more important (> 60 %) for N2O production in aquaculture ponds. The availability of nitrite is likely a major factor driving partial denitrification for both sedimentary and water column N2O production.

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Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson's disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103+/- and/or TAU368+/- transgenic mouse models, eliciting behavioral defects. Gut pathology was initially observed, and α-Syn or Tau pathology was subsequently propagated into the DMV or NTS and then to other brain regions. Remarkably, more extensive spreading and widespread neuronal loss were found in double transgenic mice (Both) than in single transgenic mice. Truncal vagotomy and α-Syn deficiency significantly inhibited synucleinopathy or tauopathy spreading. The α-Syn PET tracer [18F]-F0502B detected α-Syn aggregates in the gut and brain. Thus, α-Syn and Tau co-pathology can propagate from the gut to the brain, triggering behavioral disorders.

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BACKGROUND: Traditional methods cannot clearly visualize esophageal cancer (EC) tumor contours and metastases, which limits the clinical application of da Vinci robot-assisted surgery. AIM: To investigate the efficacy of the da Vinci robot in combination with nanocarbon lymph node tracers in radical surgery of EC. METHODS: In total, 104 patients with early-stage EC who were admitted to Liuzhou worker's Hospital from January 2020 to June 2023 were enrolled. The patients were assigned to an observation group (n = 52), which underwent da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) with the intraoperative use of nanocarbon tracers, and a control group (n = 52), which underwent traditional surgery treatment. The operation time, intraoperative blood loss, postoperative drainage tube indwelling time, hospital stay, number of lymph nodes dissected, incidence of complications, and long-term curative effects were comparatively analyzed. The postoperative stress response C-reactive protein (CRP), cortisol, epinephrine (E) and inflammatory response interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were evaluated. RESULTS: Compared with the control group, the observation group had significantly lower postoperative CRP, cortisol, and E levels (P < 0.05) with a milder inflammatory response, as indicated by lower IL-6, IL-10, and TNF-α levels (P < 0.05). Patients who underwent RAMIE had less intraoperative blood loss and shorter operation times and hospital stays than those who underwent traditional surgery. The average number of dissected lymph nodes, time of lymph node dissection, and mean smallest lymph node diameter were all significantly lower in the observation group (P < 0.05). The rate of postoperative complications was 5.77% in the observation group, significantly lower than the 15.38% observed in the control group. Furthermore, the lymphatic metastasis rate, reoperation rate, and 12- and 24-month cumulative mortality in the observation group were 1.92%, 0%, 0%, and 0%, respectively, all of which were significantly lower than those in the control group (P < 0.05). CONCLUSION: The treatment of EC using the da Vinci robot combined with nanocarbon lymph node tracers can achieve good surgical outcomes and demonstrates promising clinical applications.

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Tracer tests are an important tool for characterizing and monitoring subsurface reservoir properties. However, they are limited both because of the tracer molecules constraining factors such as irreversible adsorption, retention, and degradations, i.e. interaction processes of fluorophore molecule with surrounding media resulting in a large variation in transport properties. Elaborate tests utilizing more than one tracer to distinguish time or location of injection are complex and interpretation is ambiguous because each tracer interacts differently. In this study, we present an approach to increase tracer stability and enhance the transport uniformity of different tracers, thus making tests utilizing multiple tracers simpler and more feasible. We present this concept of tracer multiplicity by encapsulating an anionic, cationic or amphoteric fluorophore inside mesoporous silica nanoparticle carriers coated with a protective titania layer. Upon encapsulation, increased thermal resistance and drastically lowered sorption affinity towards quartz sand was detected in batch and flow-through experiments. An additional advantage of the presented nanoparticle tracers over molecular tracers is their modularity, which is demonstrated by surface modifications and application of additives that greatly reduce sorption and increase recovery rates in the flow experiments. With the here presented concept of tracer multiplicity, we introduce a new approach for colloidal tracer design that has the potential to expand and enhance measurable parameters, measurement accuracy and simplicity of analysis.

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To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow (CBF), cerebral oxygen metabolism rate (CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs.

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BACKGROUND: This study aimed to develop a novel positron emission tomography (PET) tracer, [68Ga]Ga-TD-01, for CXCR4 imaging. To achieve this goal, the molecular scaffold of TIQ15 was tuned by conjugation with the DOTA chelator to make it suitable for 68Ga radiolabeling. METHODS: A bifunctional chelator was prepared by conjugating the amine group of TIQ15 with p-NCS-Bz-DOTA, yielding TD-01, with a high yield (68.92%). TD-01 was then radiolabeled with 68Ga using 0.1 M ammonium acetate at 60 °C for 10 min. A 1-h dynamic small animal PET/MRI study of the labeled compound in GL261-luc2 tumor-bearing mice was performed, and brain tumor uptake was assessed. Blocking studies involved pre-administration of TIQ15 (10 mg/kg) 10 min before the PET procedure started. RESULTS: [68Ga]Ga-TD-01 exhibited a radiochemical yield (RCY) of 36.33 ± 1.50% (EOS), with a radiochemical purity > 99% and a molar activity of 55.79 ± 1.96 GBq/µmol (EOS). The radiotracer showed in vitro stability in PBS and human plasma for over 4 h. Biodistribution studies in healthy animals revealed favorable kinetics for subsequent PET pharmacokinetic modeling with low uptake in the brain and moderate uptake in lungs, intestines and spleen. Elimination could be assigned to a renal-hepatic pathway as showed by high uptake in kidneys, liver, and urinary bladder. Importantly, [68Ga]Ga-TD-01 uptake in glioblastoma (GBM)-bearing mice significantly decreased upon competition with TIQ15, with a baseline tumor-to-background ratios > 2.5 (20 min p.i.), indicating high specificity. CONCLUSION: The newly developed CXCR4 PET tracer, [68Ga]Ga-TD-01, exhibited a high binding inhibition for CXCR4, excellent in vitro stability, and favorable pharmacokinetics, suggesting that the compound is a promising candidate for full in vivo characterization of CXCR4 expression in GBM, with potential for further development as a tool in cancer diagnosis.

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This study investigates particle size segregation within the powder chamber of a vacuum drum-based capsule filling machine using various stirrer types and proposing novel designs to mitigate segregation. The stirrer is essential to the process, ensuring uniform density during volume-based filling. Three lactose grades, comprising 10% fine, 80% medium, and 10% coarse particles, were used, with tracer particles replacing fine or coarse particles, respectively. Dosages were collected over time for a line-array of five bores, and tracer concentrations were analysed using UV-Vis spectrophotometry. By visual assessments and stagnant zone observations particle segregation was evaluated and quantified by normalised tracer concentrations. Both standard and modified stirrers were examined under the same conditions. Stirrer type significantly influenced particle segregation, with the "spike" standard stirrer yielding the highest segregation, while the modified "3-wirem" and "coreless 3-wirem" stirrers exhibited superior performance, minimizing differences between fine and coarse particle concentrations and eliminating stagnant zones. These findings highlight promising prospects for further analysing the "3-wirem" and "coreless 3-wirem" stirrers. In that respect additional variables such as stirrer speed, rotation direction, and level of vacuum, need to be considered. Stirrer design significantly impacts vacuum drum-based capsule filling machine performance, ensuring reliable pharmaceutical capsule filling. This study offers insights into optimizing the industrial process.

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The use of the rare earth element gadolinium (Gd) in contrast agents for magnetic resonance imaging has led to a significant (micro-)contamination of riverine and coastal environments in many parts of the world. This study comprises a detailed investigation on the rare earth elements and yttrium inventory of the North Sea and also reports data for the major tributaries Thames, Rhine, Ems, Weser and Elbe. We show that large parts of the southern North Sea, including the Wadden Sea UNESCO Natural World Heritage site, are (micro)contaminated with Gd from Gd-based contrast agents (GBCA). Their dispersion reveals their estuarine input and allows to effectively track water masses and currents. The chemical persistence and conservative behavior of GBCA, coupled with the low detection limits of state-of-the-art analytical methods, makes the anthropogenic Gd a sensitive screening proxy for monitoring similarly stable, but potentially hazardous, persistent chemical/pharmaceutical substances in natural waters.

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Atmospheric nitrogen (N) deposition has notably increased since the industrial revolution, doubling N inputs to terrestrial ecosystems. This could mitigate N limitations in forests, potentially enhancing productivity and carbon sequestration. However, excessive N can lead to forest N saturation, causing issues like soil acidification, nutrient imbalances, biodiversity loss, increased tree mortality and a potential net greenhouse gas emission. Traditional experiments often overlook the canopy's role in N fate, focusing instead on direct N addition to the forest floor. In our study, we applied 20 kg N ha y-1 of labeled 15NH415NO3 solution (δ15N = 30‰) both above and below the canopy, maintaining also control plots. We assessed ecosystem components before and after treatment, calculated N stocks, and used mass balance for fertilizer recovery analysis. Findings revealed that the above-canopy N addition intercepted up to 31 ± 4% of added N in foliage, a significant contrast to the negligible recovery in leaves with below-canopy treatment. Overall plant recovery was higher in the above-canopy treatment (43 ± 11%) compared with below (9 ± 24%). Post-vegetative season, about 15 ± 1% of above-canopy added N was transferred to soil via litterfall, indicating substantial N reabsorption or loss through volatilization, stemflow or throughfall. In contrast, the below-canopy approach resulted in just 4.0 ± 0.6% recovery via litterfall. These results highlight a significant difference in N fate based on the application method. Nitrogen applied to the canopy showed distinct recovery in transient compartments like foliage. However, over a few months, there was no noticeable change in N recovery in long-lived tissues across treatments. This implies that N application strategy does not significantly alter the distribution of simulated wet N deposition in high Carbon/N tissues, underscoring the complex dynamics of forest N cycling.

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BACKGROUND: Since October 2018, lymph node status has become part of the FIGO staging, given that it is one of the most important prognostic factors among women with CC. The aim was to determine the rate of atypical lymphatic drainage in patients with clinical early-stage cervical cancer using a hybrid tracer (ICG-99mTc nanocolloid). METHODOLOGY: A prospective, observational, single-centre study conducted at Son Espases University Hospital between January 2019 and October 2023. Patients with clinical early-stage CC who underwent SLN mapping were included. External iliac and obturator nodes were defined as common locations. Para-aortic, common iliac, presacral, internal iliac, and parametrial nodes were defined as atypical locations. RESULTS: Thirty-nine cases of CC were included. The overall SLN detection rate was 97.4%, with 89.5% bilaterally. Positive nodes were found in 21.1% of patients. Atypical lymphatic drainage was present in 8 out of 38 (21.1%) patients. Of all the SLNs biopsied (146), 10.3% corresponded to an atypical zone. SLN in the atypical area had a higher proportion of metastasis than the usual area (37.5% vs. 16.7%; p = 0.327). CONCLUSIONS: SLN biopsy can detect unusual drainage in a significant proportion of patients. Atypical lymph nodes have a higher percentage of metastasis, which consequently improves staging and tailoring therapy. SLN mapping performed via a standardized surgical technique using a hybrid tracer (ICG-99mTc) could help in the identification of the "true SLN".

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Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four 18F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib. All four probes were characterized by cellular uptake studies with U87 glioma cells harboring a heterozygous IDH1 mutation (U87-mIDH) and the corresponding wildtype cells (U87-WT). In addition, the most promising probe was evaluated by PET imaging in healthy mice and mice bearing subcutaneous U87-mIDH and U87-WT tumors. Although all four probes inhibited mIDH1 with variable potencies, only one of them ([18F]mIDH-138) showed significantly higher in vitro uptake into U87-mIDH compared to U87-WT cells. In addition, PET imaging with [18F]mIDH-138 in mice demonstrated good in vivo stability and low non-specific uptake of the probe, but also revealed significantly higher uptake into U87-WT compared to U87-mIDH tumors. Finally, application of a two-tissue compartment model (2TCM) to the PET data indicated that preferential tracer uptake into U87-WT tumors results from higher specific binding rather than from differences in tracer perfusion. In conclusion, these results corroborate recent findings that mIDH1-selective inhibition may not directly correlate with mIDH1-selective target engagement and indicate that in vivo engagement of wildtype and mutated IDH1 may be governed by factors that are not faithfully reproduced by in vitro assays, both of which could complicate development of PET probes.

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Forests are the largest carbon sink in terrestrial ecosystems, and the impact of nitrogen (N) deposition on this carbon sink depends on the fate of external N inputs. However, the patterns and driving factors of N retention in different forest compartments remain elusive. In this study, we synthesized 408 observations from global forest 15N tracer experiments to reveal the variation and underlying mechanisms of 15N retention in plants and soils. The results showed that the average total ecosystem 15N retention in global forests was 63.04 ± 1.23%, with the soil pool being the main N sink (45.76 ± 1.29%). Plants absorbed 17.28 ± 0.83% of 15N, with more allocated to leaves (5.83 ± 0.63%) and roots (5.84 ± 0.44%). In subtropical and tropical forests, 15N was mainly absorbed by plants and mineral soils, while the organic soil layer in temperate forests retained more 15N. Additionally, forests retained more N 15 H 4 + $$ {}^{15}\mathrm{N}{\mathrm{H}}_4^{+} $$ than N 15 O 3 - $$ {}^{15}\mathrm{N}{\mathrm{O}}_3^{-} $$ , primarily due to the stronger capacity of the organic soil layer to retain N 15 H 4 + $$ {}^{15}\mathrm{N}{\mathrm{H}}_4^{+} $$ . The mechanisms of 15N retention varied among ecosystem compartments, with total ecosystem 15N retention affected by N deposition. Plant 15N retention was influenced by vegetative and microbial nutrient demands, while soil 15N retention was regulated by climate factors and soil nutrient supply. Overall, this study emphasizes the importance of climate and nutrient supply and demand in regulating forest N retention and provides data to further explore the impacts of N deposition on forest carbon sequestration.

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