Search Results (1,511)

Accurate measurement of androgen receptor pathway inhibitors (ARPIs) and their active metabolites is essential for pharmacokinetic studies and therapeutic drug monitoring (TDM) in patients with prostate cancer (PC). However, their simultaneous determination in human plasma is analytically challenging because of the wide concentration ranges. This study aimed to develop and validate a sensitive and robust LC–MS/MS method for the quantification of abiraterone, Δ4-abiraterone, enzalutamide, N-desmethyl enzalutamide, darolutamide, keto-darolutamide, apalutamide, and N-desmethyl apalutamide in human plasma. Sample preparation was performed by protein precipitation, followed by chromatographic separation and detection using multiple reaction monitoring with isotopically labeled internal standards (total run time 6.5 min). The method was validated in accordance with regulatory guidelines by assessing selectivity, linearity, sensitivity, accuracy, precision, recovery, matrix effects, and stability. The assay demonstrated good linearity (≥0.997) across clinically relevant concentration ranges, with lower limits of quantification between 0.1 and 40 ng/mL, depending on the analyte. Intra- and inter-day precision and accuracy were within acceptable limits, and recovery and matrix effects were consistent across different plasma matrices. Stability experiments conducted in plasma and whole blood provided practical guidance for sample handling. The method was successfully applied to 79 plasma samples from 61 patients with metastatic PC. Measured concentrations were generally consistent with published pharmacokinetic data, while unexpectedly high ABI levels were observed. Sample collection occurred between 1 and 28 h after the last drug intake, enabling assessment of the analytical method across the entire pharmacokinetic profile. Full article

The comprehensive analysis of stable carbon isotopes in dissolved organic carbon (δ¹³C-DOC) and dissolved inorganic carbon (δ¹³C-DIC) is essential for understanding carbon cycling in groundwater systems. This study evaluated the performance, stability, and accuracy of a Total Organic Carbon analyzer coupled with Cavity Ring-Down Spectroscopy (TOC-CRDS) for the determination of δ¹³C-DOC and δ¹³C-DIC. Long-term stability tests using solid standards (acetanilide) demonstrated an average precision of 0.21‰ over five days, though initial instrument stabilization was found to be critical. Systematic sensitivity experiments revealed a strong dependence of isotopic accuracy on carbon mass. For liquid samples, a minimum carbon threshold of 50 μg C (equivalent to 6.25 mg/L DOC in an 8 mL injection) was established; above this threshold, analytical precision consistently remained better than 0.3‰. Validation using synthetic samples showed excellent agreement between measured and calculated values for both DOC and DIC. Furthermore, comparative analysis of natural groundwater samples revealed that TOC-CRDS results were highly consistent with those obtained by GasBench–Isotope Ratio Mass Spectrometry, with relative deviations within 5% for DOC and 6% for DIC. The study confirms that TOC-CRDS provides a robust, high-precision (<0.3‰), and cost-effective alternative to mass spectrometry for analyzing groundwater carbon isotopes, provided that sample carbon content exceeds the determined thresholds and appropriate calibration strategies are employed. Full article

The development of sustainable and environmentally benign N-methylation methodologies is essential for enhancing sustainable synthetic practice in pharmaceutical manufacturing. In this study, we demonstrate that microwave heating (MWH) markedly enhanced the efficiency of cobalt-catalyzed N-methylation using methanol or methanol-d₄ as green C1 sources. Compared with conventional heating (CH), MWH enabled highly efficient syntheses of key pharmaceutical intermediates—including 6-dimethylamino-1-hexanol, imipramine hydrochloride, and butenafine hydrochloride—under milder conditions and shorter reaction times and without generating hazardous halogen-containing waste. UV–vis spectroscopic analysis revealed that MWH accelerated the transformation of Co(acac)₂ into catalytically active Co species by approximately four-fold, providing a mechanistic basis for the enhanced reactivity. We hypothesized that this effect was caused by the selective microwave heating of the catalyst, which in turn promoted the rapid generation of catalytically active species. Notably, MWH also significantly improved the N-trideuteromethylation of amines using methanol-d₄, achieving a 95% yield for imipramine-d₃ hydrochloride versus 32% under CH. Molecular dynamics simulations indicated that methanol-d₄ exhibited slower dipole relaxation and enhanced cluster fragmentation under microwave fields, improving catalyst–substrate contact, while kinetic isotope effects stabilized reactive intermediates. These synergistic effects account for the pronounced microwave promotion observed in deuterated systems. Overall, the combination of MWH and cobalt catalysis offers an energy-efficient, waste-minimizing, and environmentally benign strategy for the scalable synthesis of both methylated and deuterated amines. Full article

Background: Accurate axillary staging is vital in breast cancer. While dual tracers (Tc-99m + methylene blue dye) are standard for sentinel lymph node biopsy (SLNB), indocyanine green (ICG) offers a cost-effective, safe alternative, especially where nuclear medicine access is limited. Despite growing global use, data from low- and middle-income countries (LMICs) remain scarce. This study presents India’s largest cohort using ICG in SLNB. Methods: We analyzed data from 678 breast cancer patients (2013–2023), of whom 609 underwent SLNB. For analysis, patients were grouped into: isotope + blue dye (control), ICG + blue dye (study group), and ICG alone. False-negative rate (FNR) was evaluated in cases where SLNB was followed by axillary lymph node dissection (ALND). All other outcomes were assessed across the SLNB cohort. Results: In upfront surgery, the study group had an identification rate (IR) of 95.6%, an FNR of 5%, and a median node yield of four, compared to the control group (IR 94.1%, FNR 0%, median of three). Post-neoadjuvant systemic therapy (NAST), the study group outperformed the control (IR 92% vs. 88.2%; both FNR 10%), with higher node yield (three vs. two). From 2021, ICG alone showed 100% IR, 0% FNR (upfront), and 95.6% IR (post-NACT), with high median node retrieval. Overall recurrence was 7.8%; loco-regional recurrence was 3.09%. Conclusions: ICG offers high efficacy, safety, and feasibility as a sole tracer, especially in LMICs. Its integration into SLNB and oncoplastic workflows supports its broader adoption as a practical alternative to radioisotopes in breast cancer surgery. Full article

Surface water–groundwater interactions within oasis–desert ecotones of arid regions play a pivotal role in sustaining regional water security and ecological stability. Taking the Niya River Basin in Xinjiang, Northwest China, as a representative inland watershed, this study systematically elucidates the mechanisms and seasonal dynamics of surface water–groundwater coupling under the combined influences of natural processes and anthropogenic activities. A total of 68 surface water and groundwater samples were collected during the dry, normal, and wet hydrological periods. Integrated hydrochemical characterization, mineral saturation index analysis, and stable isotope (δ²H and δ¹⁸O) mass balance modeling were employed to quantify recharge contributions and unravel hydrogeochemical evolution pathways. Results indicate that the waters in the study area are predominantly brackish to saline, with consistent dominant ionic assemblages (SO₄²⁻ and Na⁺) across all hydrological periods, highlighting evaporite dissolution as the primary control on solute composition. Hydrochemical evolution is jointly regulated by evaporation concentration, water–rock interactions, and cation exchange processes. Surface water chemistry reflects the combined effects of silicate weathering and evaporite dissolution, whereas groundwater chemistry is mainly governed by evaporite dissolution coupled with pronounced cation exchange. Stable isotope signatures reveal substantial secondary evaporation of regional precipitation prior to recharge. Frequent bidirectional recharge between surface water and groundwater was observed, exhibiting distinct seasonal transitions. During the dry period, groundwater provides significant baseflow support to surface water (48.6% in the oasis zone and 54.3% in the desert zone). In the normal period, recharge direction reverses, with surface water becoming the dominant source of groundwater recharge (99.0% in the oasis zone and 76.6% in the desert zone). In the wet period, spatial heterogeneity becomes evident: surface water continues to dominate groundwater recharge in the oasis zone (92.7%), whereas groundwater recharge to surface water prevails in the desert zone (50.5%). This study identifies a seasonally dynamic “discharge–infiltration–zonal regulation” bidirectional recharge pattern in arid inland river systems. The findings advance the mechanistic understanding of hydrological connectivity reconstruction within oasis–desert ecotones and provide a scientific basis for optimized regional water resource allocation and groundwater salinization risk mitigation. Full article

Diopside–hedenbergite solid solution is the most common clinopyroxene end-member combination in mafic and ultramafic igneous rocks. The crystal structure variety caused by Mg-Fe isomorphous substitution can indicate geological processes such as Mg-Fe isotope fractionation. To explore the effect of Hubbard U correction and Fe content on iron-bearing clinopyroxene structures, we employed GGA and GGA + U to study the lattice constants, unit-cell volume, and average Fe-O bond length of the diopside–hedenbergite solid solution series. On the whole, the results by GGA + U are the increase in lattice constant a (from 9.910 Å to 10.030 Å) and volume (from 456.656 ų to 464.640 ų), the decrease in β angle (from 106.121°to 105.320°), and a slight variation in the lattice constant b (from 9.007 Å to 9.010 Å) with increasing Fe content, which is a better match with the experiment than those by GGA. The average Fe-O bond lengths and polyhedral volumes calculated by GGA and GGA + U both increase with increasing Fe content. The Hubbard U correction significantly affects the lattice constants and unite-cell volume at medium-high Fe content (Fe/(Ca+ Mg + Fe) > 2/8), the Fe-O bond at low Fe content (Fe/(Ca+ Mg + Fe) < 1/8), the bond angle variance, distortion index and quadratic elongation at relatively medium Fe content (1/8 ≤ Fe/(Ca+ Mg + Fe) ≤ 5/16). This study verifies the effectiveness of U-value correction on iron-bearing clinopyroxene and provides a theoretical basis for understanding its structural evolution. Full article

To elucidate the regulatory mechanisms underlying the interaction between straw return and nitrogen (N) fertilization on yield formation, nutrient uptake, and soil N cycling in a continuous maize cropping system, a two-year positioning experiment was conducted. The study established two straw treatments (S0: 0 g/box; S1: 84 g/box) combined with three N levels (N0: 0 g/box; N1: 1.24 g/box; N2: 2.47 g/box). (The box refers to the cylinder used for planting maize.) The responses of maize yield, plant nutrient accumulation and partitioning, fertilizer-derived N ratio, nitrogen fertilizer use efficiency (NUE), and soil microenvironment were analyzed. Results indicated that under N1 conditions, straw return had a negligible effect on crop growth and yield formation. Conversely, under N2 conditions, straw return significantly enhanced maize yield and promoted the accumulation of N, phosphorus (P), and potassium (K) in plant tissues. ¹⁵N isotope tracing revealed a novel mechanism: rather than significantly altering direct fertilizer nitrogen use efficiency, straw return improved crop yield primarily by elevating indigenous soil N content and boosting the activities of N-transforming enzymes, thereby beneficially altering the ultimate environmental fate of the fertilizer N. Furthermore, straw return significantly boosted the activities of enzymes involved in N transformation and optimized the soil microenvironment. Collectively, straw return coupled with increased N application (specifically the S1N2 treatment) significantly maximizes maize yield, providing a theoretical basis for rational straw utilization and N management. Full article

Accurately tracing the geographical origin of Zanthoxylum schinifolium Sieb. et Zucc. is important for brand authentication, quality control, and food safety assurance. In this study, the stable isotope ratios (δ¹³C, δ¹⁵N, δ²H, δ¹⁸O) and the contents of 20 elements were analyzed in samples from three major production regions. Significant differences (p < 0.05) were observed in δ¹³C, δ²H, δ¹⁸O and most elemental profiles across origins. Chemometric methods—including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and linear discriminant analysis (LDA)—were applied to classify samples by geographical origin. OPLS-DA identified key discriminators (VIP > 1) such as Ca, δ¹³C, Mg, δ²H, B, δ¹⁸O, Cr, Ni, Na, Pb, As, Co, Se, and Zn, achieving a classification accuracy of 96.8%. LDA based on the combined isotope and element datasets showed even higher performance, with an original discrimination rate of 98.4% and a cross-validated rate of 92.8%. The results demonstrate that integrating stable isotope and multi-element fingerprints with supervised classification models provides a reliable and effective approach for verifying the geographical origin of Zanthoxylum schinifolium, supporting its use in traceability systems and fair trade practices. Full article

Background/Objectives: The aztreonam/avibactam combination represents a promising therapeutic option for severe infections caused by multidrug-resistant Gram-negative pathogens, particularly in critically ill patients. Due to marked pharmacokinetic variability and the need to achieve joint pharmacokinetic/pharmacodynamic (PK/PD) targets of both agents, therapeutic drug monitoring (TDM) may play a pivotal role in optimizing treatment. This study aimed to develop and validate two rapid, accurate, and sensitive UHPLC–qTOF MS/MS sequential methods for quantifying aztreonam and avibactam in human plasma, suitable for routine clinical TDM. Methods: Plasma concentrations were determined by means of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC–qTOF MS/MS), operating in positive and negative electrospray ionization modes for aztreonam and avibactam, respectively. Sample preparation consisted of protein precipitation with isotopically labeled internal standards. The method’s validation was performed according to the European Medicines Agency guidelines, by assessing selectivity, linearity, precision, accuracy, recovery, matrix effects, carry-over, and stability. Clinical applicability was evaluated by reprocessing plasma samples, which were already previously collected for routine clinical practice from 20 hospitalized patients undergoing treatment with ceftazidime-avibactam plus aztreonam. Results: The methods showed excellent linearity (R² ≥ 0.999) over ranges of 0.2–100 µg/mL for aztreonam and 0.1–50 µg/mL for avibactam. Lower limits of quantification were 0.2 µg/mL and 0.1 µg/mL, respectively. Intra- and inter-day precision and accuracy met the EMA criteria at all of the quality control levels. Extraction recovery exceeded 90% for both analytes, and matrix effects were effectively compensated by internal standards. Stability testing highlighted the need for careful sample handling, particularly for aztreonam under repeated freeze–thaw conditions. Clinical application revealed substantial inter-individual variability in steady-state concentrations. Conclusions: The validated UHPLC–qTOF MS/MS assays provide robust and sensitive sequential quantification of aztreonam and avibactam in human plasma, supporting TDM-guided dose optimization in clinical practice. Full article

This study is based on isotope (δ¹⁸O, δ²H, ¹⁴C), hydrochemical, and groundwater-level data from the past 47 years in the central North China Plain (NCP). It uses methods such as mathematical statistics, Piper diagrams, Gibbs models, and ion ratios to investigate the characteristics of changes in the groundwater flow field, hydrochemistry, and isotopes across various aquifers in the Hengshui funnel area before and after the implementation of groundwater exploitation reduction measures (GWER). Furthermore, it reveals the driving mechanisms of these measures’ effects on hydrochemical characteristics and isotopic variations. The results show the following: (1) The hydrochemical type of shallow groundwater (SG) before GWER was primarily Cl▪SO₄-Na▪Ca, which diversified to Cl▪SO₄-Na and SO₄▪Cl-Na types after GWER; the deep groundwater (DG) type changed from Cl▪SO₄-Na to Cl-Na. (2) Before GWER, the hydrochemical composition of SG and DG was primarily controlled by the dissolution of silicates, salt rocks, and evaporites. After GWER, the hydrochemical composition of DG primarily originated from the dissolution of evaporites and salt rocks, accompanied by enhanced cation exchange. (3) The δ¹⁸O of SG was affected by the recharge of irrigation return water, changing from enrichment to depletion before and after the GWER. The δ¹⁸O value in DG changed from depletion to enrichment, and the groundwater age changed from older to younger after the GWER. The GWER altered the hydrodynamics, weakened the hydraulic connectivity, and led to changes in the evolution of the hydrochemistry. The findings have direct implications for water quality and promoting the sustainable utilization of deep groundwater in the NCP’s central funnel area. Full article

Kelp transplantation is a nature-based strategy aimed at restoring coastal habitat integrity and marine biodiversity. However, its functional consequences for trophic integration within benthic food webs remain poorly understood. Using δ¹³C and δ¹⁵N stable isotope analyses, we evaluated how Undaria pinnatifida transplantation alters consumer trophic structures and isotopic niche characteristics in Oeyeondo, South Korea. While basal source remained isotopically uniform across sites, the introduction of U. pinnatifida triggered significant isotopic shifts in consumers, reflecting a reorganization of carbon assimilation pathways. At the transplanted site, herbivores exhibited significantly enriched δ¹³C values (−14.7 ± 2.0‰ to −13.2 ± 0.3‰) compared to the control site (−19.3 ± 1.2‰), indicating direct assimilation of kelp-derived carbon. Conversely, grazers showed depleted δ¹³C values (−20.6 ± 0.6‰) reflecting a shift toward alternative benthic resources. Isotopic niche metrics revealed a broader community-level niche width at the transplanted site, driven by increased resource diversity and niche partitioning. These findings demonstrate that kelp transplantation effectively restructures benthic food web dynamics by providing new energy pathways, offering a robust functional framework for evaluating marine forest restoration success. Full article

Groundwater used for drinking in settlements located near decommissioned uranium mining facilities may contain elevated naturally occurring radioactive materials, posing long-term public-health concerns. The purpose of this study was to evaluate the radiological quality of groundwater used for drinking in the Saumalkol settlement by applying gross alpha–beta screening and isotope-specific analysis of ²²⁶Ra and ²²⁸Ra to identify the main contributors to groundwater radioactivity and estimate the associated radiation dose from water consumption. Groundwater samples were analyzed using gross alpha–beta screening and isotope-specific determination of ²²⁶Ra and ²²⁸Ra by radiochemical separation and low-background counting, and ingestion doses were estimated using international dose coefficients. Gross alpha activity averaged 2.26 ± 0.96 Bq/L, with most samples exceeding the WHO screening value of 0.5 Bq/L, while gross beta activity averaged 0.65 ± 0.17 Bq/L. Mean activity concentrations of ²²⁶Ra and ²²⁸Ra were 0.17 ± 0.03 Bq/L and 1.47 ± 0.9 Bq/L, respectively, with significantly higher ²²⁸Ra in deep boreholes and a systematic predominance of ²²⁸Ra over ²²⁶Ra (p < 0.05), indicating a thorium-controlled geochemical signature in fractured crystalline aquifers. The estimated annual committed effective ingestion dose from radium isotopes was 0.46 mSv, exceeding the reference level of 0.1 mSv for drinking-water exposure. These findings demonstrate that groundwater radioactivity in Saumalkol is dominated by radium from the thorium series and highlight the need for sustained radionuclide-specific monitoring and targeted water management strategies in uranium-affected regions. Full article

Optimizing public investment in urban green infrastructure under water scarcity is a core challenge in resource economics. Against the backdrop of global climate change—characterized by rising temperatures, increased frequency and intensity of droughts, and altered precipitation patterns—this study addresses the critical knowledge gap in quantifying the economic returns on the physiological adaptations of urban trees, which are central to their value as natural capital. We integrated dual-water isotope (δ²H, δ¹⁸O) and leaf carbon isotope (δ¹³C) analyses to mechanistically decode the water use strategy of Machilus yunnanensis (M. yunnanensis) in drought-prone Kunming, China. The results show strategic seasonal plasticity: a shift from shallow soil water (10–50 cm) in the wet season to deeper soil sources (50–90 cm) and stem reserves in the dry season, coupled with a dynamic, diurnally variable water use efficiency (WUE_13C). We then constructed a transparent economic valuation model translating these traits into three quantifiable benefit streams: (1) operational cost savings (EV₁) from reduced irrigation demand; (2) enhanced marginal productivity of water (EV₂) in ecosystem service generation; and (3) climate resilience value (EV₃) via mitigated mortality risk. Our “Water–Carbon–Economy” nexus framework provides a generalizable methodology for assessing the cost-effectiveness and risk-adjusted returns of urban forest species, demonstrating that tree selection based on such eco-efficient traits is not merely an ecological choice but a sound economic investment, offering direct implications for budget-constrained municipalities seeking to maximize green infrastructure benefits under climate uncertainty. Full article

Matrix effects (ME) during LC-ESI-MS analysis are a commonly acknowledged issue for a variety of matrices and analytes. Although sample preparation techniques are steadily evolving to reduce ME, the complexity and variability of the urine matrix remain a challenge, especially for multi-analyte methods. To investigate the extent of ME implications on method performance and quantification, we used stable isotope-labelled standards (SIL-IS) of 11 mycotoxins to evaluate the magnitude and variability of ME in urine samples from two cohorts: Bangladeshi adult women (n = 50) and Swedish children of both sexes (n = 340). Significant ME differences were observed between the two cohorts for eight of the 11 mycotoxins. Additionally, intra-cohort ME variability turned out to be very high with interquartile ranges (IQR) above 15% for 14 out of 22 analyte-cohort combinations. Maximum IQR values were observed for sterigmatocystin in the Bangladeshi cohort (318%), strongly impacting quantitative results obtained with matrix(-matched) calibration. Further experiments on a small German cohort of four subjects, each providing four to five urine samples, revealed high variability of ME within each individual. Factors influencing ME were investigated, showing little to no impact of sex and a moderate impact of age for some analytes in the Swedish cohort. Nonetheless, especially the more polar analytes, showing stronger signal suppression, demonstrated clear correlation of ME with density and creatinine concentration of the urine samples. As a result, urine samples with very high or low density or creatinine values require careful handling in regard to sensitivity or quantification errors when matrix(-matched) calibration without SIL-IS is applied. Full article

Advanced oxidation technology utilizing ozone as the oxidant shows great potential for the efficient purification of wastewater. However, the efficiency of ozone decomposition remains a significant bottleneck limiting the performance of ozone-based advanced oxidation processes. Catalytic ozone decomposition technology is a highly effective approach to enhancing ozone utilization efficiency; nevertheless, the competing adsorption of water molecules results in low catalytic reaction efficiency and catalyst deactivation. In this study, NiFe layered double hydroxide (LDH) was prepared successfully through the hydrothermal method. In situ DRIFTS with isotope labeling revealed that ozone combines with surface H atoms to produce H₂O, whereas the oxidation of high-valence metals destroys H₂O, producing H atoms that return to the surface of NiFe LDH. The unique structure of NiFe LDH allows water to participate in the surface H atom cycle process, and the charge exchange between Ni and Fe atoms accelerates the recovery of surface H atoms, which avoids the deactivation of the active site caused by competitive adsorption of water molecules, achieving a catalytic ozone decomposition efficiency of 99% for 80 h and 59.0% for simulated wastewater containing polyacrylamide as a model pollutant. This work presents a fresh insight into surface H cycling of LDH materials to improve the wet resistance of the catalysts. Full article