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Voxelotor was approved for the treatment of sickle cell anemia as a potent hemoglobin S polymerization inhibitor. Owing to its ability to affect blood components and its potential to enhance athletic performance, voxelotor was included in the prohibited list issued by the World Anti-Doping Agency in 2023, banning its use both in and out of competition. This study aimed to comprehensively investigate the metabolic profile of voxelotor in human urine and identify suitable metabolites for long-term analytical retrospectivity in doping control. A novel strategy for metabolite identification was established by combining in vivo human administration with isotope labeling-based in vitro metabolism analysis. A single microdose of voxelotor was administered orally to five volunteers, and urine samples were collected for up to 28 days post-administration. Concurrently, in vitro incubation of human liver microsomes with voxelotor and D3-voxelotor was conducted, and the microsomal incubates were analyzed via liquid chromatography-high-resolution mass spectrometry. Targeted metabolite searches in human urine samples and automated nontargeted screening of isotope metabolite ion pairs in incubation samples led to the discovery of 9 phase I metabolites and 23 phase II metabolites. Analysis of the urine excretion curves revealed that 4 metabolites, along with voxelotor, were suitable for long-term anti-doping monitoring, with a detection window exceeding 20 days. Using both in vivo and in vitro metabolic models, this study provides comprehensive insight into the metabolic profile of voxelotor in human urine for the first time, enhancing the capacity for doping screening and extending the retrospectivity of voxelotor detection.

Toxic milk (txJ) is an autosomal recessive mutation in the Atp7b gene in the C3H/HeJ strain, observed at The Jackson Laboratory in Maine, USA. TxJ mice exhibit symptoms similar to those of human Wilson's disease (WD). The study aimed to verify organ involvement in a mouse model of WD. TxJ mice and control animals were sacrificed at 2, 4, 8, and 14 months of age. Total X-ray Fluorescence Spectroscopy (TXRF) was used to determine the elemental concentration in organs. Tissue chemical composition was measured by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, hybrid mapping of FTIR and microXRF was performed. Elevated concentrations of Cu were observed in the liver, striatum, eye, heart, and duodenum of txJ mice across age groups. In the striatum of the oldest txJ mice, there was lower lipid content and a higher fraction of saturated fats. The secondary structure of striatum proteins was disturbed in txJ mice. In the livers of txJ mice, higher concentrations of saturated fats and disturbances in the secondary structure of proteins were observed. The concentration of neurofilaments was significantly higher in txJ serum. The distribution of Cu deposits in brains was uniform with no prevalence in any anatomic structure in either group, but significant protein structure changes were observed exclusively in the striatum of txJ. In this txJ animal model of WD, pathologic copper accumulation occurs in the duodenum, heart, and eye tissues. Increased copper concentration in the liver and brain results in increased saturated fat content and disturbances in secondary protein structure, leading to hepatic injury and neurodegeneration.

Endometriosis is a benign gynecological disorder characterized by the abnormal presence of endometrium-like cells, referred to as ectopic tissue, located outside the uterine cavity. Beyond the abnormal proliferation of endometrium-like tissues within and beyond the pelvic cavity, compelling scientific evidence underscores the crucial involvement of the NOD-like receptor NLRP3 inflammasome and pyroptosis in the pathogenesis of EMS. Our investigation has revealed a striking upregulation of the endogenous protein GATA-binding protein 6 (GATA6) in abdominal wall EMS. Notably, the knockdown of GATA6 significantly impaired the viability and migratory potential of primary ectopic endometrial stromal cells (EESCs) while also inhibiting crucial markers of pyroptosis, such as NLRP3, the gasdermin D N-terminal fragment (GSDMD-N), and reactive oxygen species (ROS) levels within these cells. Delving deeper into the underlying mechanisms, we discovered that suppressing GATA6 mitigated the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in EESCs. The administration of 740 Y-P, an agonist of the PI3K/AKT pathway, mitigated the inhibitive actions of GATA6 knockdown on EESCs' growth, migration, and pyroptosis, highlighting the intricate crosstalk between GATA6 and this intricate signaling cascade. In vivo experiments corroborated these findings, demonstrating that reduced GATA6 expression effectively restrained the growth of endometrial lesions and concurrently suppressed pyroptosis, accompanied by a dampening of PI3K/AKT signaling within these lesions. In summary, our study underscores the pivotal role of GATA6 in modulating the growth and pyroptosis of abdominal wall EMS through its regulation of the PI3K/AKT signaling pathway. Silencing GATA6 emerges as a promising approach to alleviate pyroptosis and potentially offers a novel therapeutic angle for managing abdominal wall EMS.

Limited research has been conducted on microplastic (MP) contamination in the rivers of Goa. To address this gap, this study examines the levels of MP contamination in the surface water of the Zuari River, Goa. We investigate the abundance, characteristics (size, shape, colour, and polymer composition), and risk assessment of MPs. MPs were detected at all sampling stations in the Zuari River, with concentrations varying from 0.01 particles/L (S3) to 1.38 particles/L (S13). The average abundance of MPs in the water samples was 0.28 ± 0.35 particles/L. MPs were more common in the 0.3-1 mm size range (51.70%) than in the 1-5 mm range (48.30%). The most common MP shapes observed were fibers (37.88%) and fragments (29.66%). FTIR analysis confirmed the presence of polyethylene terephthalate, high-density polyethylene, polypropylene, and polyacrylamide carboxyl-modified MPs. The Pollution Load Index (PLI) showed an average value of 3.8, indicating significant contamination (PLI > 1). Scanning electron microscopy (SEM) revealed various degradation features such as pits, scratches, grooves, and cracks on the MPs surfaces, while energy dispersive X-ray spectroscopy (EDS) detected metals on the MP's surfaces. This study provides key insights into MP pollution in the Zuari River's surface water and lays the groundwork for future research and management strategies in the region.

This study successfully synthesized a composite photocatalyst g-C₃N₄/PbTiO₃ through hydrothermal and calcination methods using PbTiO₃ and g-C₃N₄. The catalyst was characterized by XRD, FTIR, Raman, XPS, SEM, TEM, UV-vis DRS, PL, and other techniques. The results indicate that the composite photocatalyst exhibits efficient electron transfer, enhanced light absorption, effective separation and utilization of photogenerated electron-hole pairs, demonstrating superior photocatalytic activity. Under simulated sunlight, the removal efficiency of methyl blue (MB) with an initial concentration of 10 mg/L reaches 93.0% after 120 min. After five cycles, the degradation efficiency of MB is 79.2%, still maintaining 85% of the initial catalytic activity. The pH values in the range of 4.0-7.0, inorganic anions, and water quality have a minimal impact on the photocatalytic degradation of MB. Additionally, the composite photocatalyst exhibits strong removal capabilities for other pollutants, such as tetracycline. Therefore, the prepared catalyst demonstrates good feasibility for practical applications. Free radical quenching experiments indicate that hydroxyl radicals (·OH) are the primary active groups in the photocatalytic degradation of MB. Based on this, a photocatalytic mechanism involving a S-scheme heterojunction has been proposed. This study provides new insights into preparing PbTiO₃ composite semiconductors and constructing novel S-scheme heterojunctions.

Fungal biomass is as a cost-effective and sustainable biosorbent utilized in both active and inactive forms. This study investigated the efficacy of inactivated and dried biomass of Fusarium sp. in adsorbing Ni²⁺ and Pb²⁺ from aqueous solutions. The strain underwent sequential cultivation and was recovered by filtration. Then, the biomass was dried in an oven at 80 ± 2 °C and sieved using a 0.1-cm mesh. The biosorbent was thoroughly characterized, including BET surface area analysis, morphology examination (SEM), chemical composition (XRF and FT-IR), thermal behavior (TGA), and surface charge determination (pH-PZC and zeta potential). The biosorption mechanism was elucidated by fitting equilibrium models of kinetics, isotherm, and thermodynamic to the data. The biosorbent exhibited a neutral charge, a rough surface, a relatively modest surface area, appropriate functional groups for adsorption, and thermal stability above 200 °C. Optimal biosorption was achieved at 25 ± 2 °C, using 0.05 g of adsorbent per 50 mL of metallic ion solution at initial concentrations ranging from 0.5 to 2.0 mg L^-1 and at pH 4.5 for Pb²⁺ and Ni²⁺. Biosorption equilibrium was achieved after 240 min for Ni²⁺ and 1440 min for Pb²⁺. The process was spontaneous, mainly through chemisorption, in monolayer for Ni²⁺ and multilayer for Pb²⁺, with efficiencies of over 85% for both metallic ion removal. These findings underscore the potential of inactive and dry Fusarium sp. biomass (IDFB) as a promising material for the biosorption of Ni²⁺ and Pb²⁺.

The Water Quality Index (WQI) provides comprehensive assessments in river systems; however, its calculation involves numerous water quality parameters, costly in sample collection and laboratory analysis. The study aimed to determine key water parameters and the most reliable models, considering seasonal variations in the water environment, to maximize the precision of WQI prediction by a minimal set of water parameters. Ten statistical or machine learning models were developed to predict the WQI over four seasons using water quality dataset collected in a coastal city adjacent to the Yellow Sea in China, based on which the key water parameters were identified and the variations were assessed by the Seasonal-Trend decomposition procedure based on Loess (STL). Results indicated that model performance generally improved with adding more input variables except Self-Organizing Map (SOM). Tree-based ensemble methods like Extreme Gradient Boosting (XGB) and Random Forest (RF) demonstrated the highest accuracy, particularly in winter. Nutrients (Ammonia Nitrogen (AN) and Total Phosphorus (TP)), Dissolved Oxygen (DO), and turbidity were determined as key water parameters, based on which, the prediction accuracy for Medium and Low grades was perfect while it was over 80% for the Good grade in spring and winter and dropped to around 70% in summer and autumn. Nutrient concentrations were higher at inland stations; however, it worsened at coastal stations, especially in summer. The study underscores the importance of reliable WQI prediction models in water quality assessment, especially when data is limited, which are crucial for managing water resources effectively.

This study focused on 120 specimens of the shrimp Palaemon elegans collected in intertidal zones in eight selected areas. This study aimed to assess the suitability of P. elegans as a bioindicator of natural and anthropogenic marine pollution. Metal concentrations of aluminum (Al), cadmium (Cd), copper (Cu), iron (Fe), lead (Pb), and zinc (Zn) were measured in shrimp collected from various sites in the Canary Islands, including areas affected by volcanic activity, industrial activity, and control zones. The determination of metal concentrations was conducted using inductively coupled plasma optical emission spectrophotometry (ICP-OES). The results showed significant differences in metal concentrations across the studied sites, with the highest levels of Al, Cu, Fe, Pb, and Zn observed in areas impacted by the Tajogaite volcanic eruption and harbor activity. Sites near old landfills and sewage pipes also exhibited elevated levels of Cd, Cu, and Pb, indicating strong anthropogenic influence. Al was found in the highest concentration in Harbour, reaching 25.7 ± 6.2 mg/kg, while the lowest concentration was observed in Control Lp at 11.5 ± 0.69 mg/kg. Conversely, lower metal concentrations were detected in control zones and areas with high dinoflagellate presence, suggesting a potential role of bioremediation by marine phytoplankton. The ability of P. elegans to accumulate metals in its tissues, particularly in areas of high pollution, highlights its potential as a bioindicator species. This study underscores the importance of P. elegans in monitoring marine pollution and provides insights into the environmental impact of both natural and human-induced contamination on coastal ecosystems.

The COVID-19 pandemic has prompted the medical systems of many countries to develop effective treatments to combat the high rate of infection and death caused by the disease. Within the array of proteins found in SARS-CoV-2, the 3 chymotrypsin-like protease (3CL^pro) holds significance as it plays a crucial role in cleaving polyprotein peptides into distinct functional nonstructural proteins. Meanwhile, RNA-dependent RNA polymerase (RdRp) takes center stage as the key enzyme tasked with replicating the viral genomic RNA within host cells. These proteins, 3CL^pro and RdRp, are deemed optimal subjects for QSAR modeling due to their pivotal functions in the viral lifecycle. In this study, SMILES-based QSAR classification models were developed for a dataset of 2377 compounds that were defined as either active or inactive against 3CLpro and RdRp. Pharmacophore (PH4) and QSAR modeling were used for the virtual screening on 60.2 million compounds including ZINC, ChEMBL, Molport, and MCULE databases to identify new potent inhibitors against 3CL^pro and RdRp. Then, a filter was established based on typical molecular characteristics to identify drug-like molecules. The molecular docking was also performed to evaluate the binding affinity of 156 AND 51 potential inhibitors to 3CL^pro and RdRp, respectively. Among the 15 hits identified based on molecular docking scores, M3, N2, and N4 were identified as promising inhibitors due to their good synthetic accessibility scores (3.07, 3.11, and 3.29 out of 10 for M3, N2, and N4 respectively). These compounds contain amine functional groups, which are known for their crucial role in the binding interactions between drugs and their targets. Consequently, these hits have been chosen for further biological assay studies to validate their activity. They may represent novel 3CL^pro and RdRp inhibitors possessing drug-like properties suitable for COVID-19 therapy.