Effective sulbactam dosing regimens for treating A. baumannii meningitis in pediatric patients, considering the degree of cerebrospinal fluid (CSF) inflammation and its consequent effect on drug penetration, have not been thoroughly studied. This study aimed to describe a cerebrospinal pharmacokinetic (PK) model of sulbactam and propose a dosing strategy in pediatric patients based on pharmacodynamic (PD) evaluation with stochastic simulation. Publications were systematically extracted from MEDLINE for sulbactam CSF PK data collection. A cerebrospinal PK model was described using CSF samples and applied to estimate the probability of attaining PK/PD target {60% time above the minimum inhibitory concentration [T > minimum inhibitory concentration (MIC)] in CSF}. The cerebrospinal PK/PD breakpoint was defined as the highest MIC at which target attainment probability in CSF was ≥90% for each age group [infants (4 weeks-11 months), children (1-6 years) and pediatrics (7-16 years)]. The study population included 21 pediatric patients aged 0.083-13.5 years. The CSF/serum concentration ratio at the various sampling points ranged 0.002-0.695. Based on the result of covariate analysis, CSF protein and CSF glucose levels were incorporated into the CSF-to-serum partition coefficient. The visual predictive check of CSF concentrations indicated no major bias. Regarding the cerebrospinal PK/PD evaluation, in infants and children groups with meningeal inflammation (e.g., CSF protein >100 mg/dL and CSF glucose <40 mg/dL) sulbactam dose of 200 mg/kg/day (as sulbactam component) with 0.5-h infusion were required to achieve 90% probability of CSF target attainment (60% T > MIC) up to a MIC of 4 μg/mL for A. baumanii. This study identified effective dosing regimens for A. baumannii meningitis in pediatric patients in consideration of the degree of inflammation in CSF. High-dose sulbactam regimens can be considered to optimize CSF target attainment for A. baumannii meningitis in pediatric patients.

Antibiotic resistance (AMR) is a global health crisis responsible for over five million deaths annually. Rapid antimicrobial susceptibility testing (RAST) is critical for timely clinical decision-making. This study develops a hydrogel-based 3D culture microfluidic platform enclosed within a PMMA box, enabling safe and rapid testing of highly pathogenic bacteria. The microfluidic chip employs a Christmas tree concentration gradient generator, capable of simultaneously delivering four distinct drug concentrations. Theoretical, finite-element method, and experimental analyses demonstrated precise gradient control by tuning inlet flow-rate ratios (Q1/Q0), concentration ratios (C0/C1), and absolute concentrations (C0). Optimizing hydrogel porosity (90%) and chamber height (200 μm) enhanced mass transfer, improving bacterial growth and drug delivery. Using Escherichia coli ATCC 25922 as a model, the system determined the minimum inhibitory concentration (MIC, 2 μg/mL) of gentamicin within 2 h─8 to 10-fold faster than standard methods, while matching conventional AST accuracy. From a fluid dynamics perspective, this work optimized the flow and mass transfer processes in AST, thereby enhancing the contact between nutrients, drugs, and bacteria. This hydrogel-based 3D microfluidic system provides a safe, efficient, and scalable RAST platform with strong potential for clinical applications against highly pathogenic and drug-resistant bacteria.

Epilepsy is a central nervous system disease characterized by the sudden onset of seizures, loss of consciousness, or confusion. In recent years, many non-intravenous routes of administration of benzodiazepines have been developed for seizure control, with intranasal administration being an attractive route of choice. However, for such a route of administration, there is a lack of evidence on the choice of the epilepsy drug. This study aims to compare the intranasal formulations of three first-line drugs for seizure control, namely midazolam, diazepam, and lorazepam, via an ideal intranasal treatment.A pilocarpine-induced seizure model in mice was used to compare drug efficacy. The three drugs were administered intranasally to 36 C57 mice at a single dose of 1mg/kg, followed by inducing the seizures via intraperitoneal injection of pilocarpine. The subsequent seizure scores were observed for either 10-100min. After sacrificing the mice at 10/100 minutes post-dosing, whole brain tissue and plasma were collected to analyze the drug concentrations as well as brain-to-plasma concentration ratios. In addition, effects of these intranasally delivered drugs on neuroinflammation-associated molecules were monitored and compared via the mRNA levels and/or protein expression of GABARα1, TNF-α, and IL-1β in the cortex and hippocampus. Additionally, drug bindings to plasma and brain tissue obtained using the ultrafiltration method were compared, and drug binding affinities towards the GABAA receptor, as determined via the computer docking technique, were also compared.Among the three tested drugs, our results suggested that intranasal diazepam, with the highest brain-to-plasma ratio, was the best in seizure control at 10min. Although all three drugs showed good stability, similar brain binding and receptor binding affinity, diazepam demonstrated the greatest efficacy in reducing TNF-α mRNA and protein levels, and lowest plasma protein binding, which could contribute to its higher brain-to-plasma ratio and better acute epilepsy control compared to the other two drugs.Our pilot in vivo experiments in the pilocarpine-induced mice seizure model for the first time demonstrated that intranasally administered benzodiazepines are effective for seizure control at the early stage, with intranasally delivered diazepam being the most potent one.

Whales contribute to novel insight on poly- and perfluoroalkyl substances bioaccumulation in the East China sea.

In vivo evidence of functional OATP2B1 activity in human skeletal muscle using [11C]erlotinib PET.

Determination of transfer factors for 90Sr and stable Sr from soil to plants in semi-arid regions of Türkiye.

Shelling is a vital procedure in shrimp processing. This study demonstrated how different shelling methods affected shrimp muscle quality during refrigeration. Results showed that the microstructure of the frozen (F) and enzyme-treated (E) groups was damaged, while the slurry ice (SI) group remained unchanged compared to the control (CK). During storage, all groups experienced significant decreases in muscle elasticity, hardness, Ca2+-ATPase activity, and sulfhydryl value, along with increases in TCA-soluble peptide levels, surface hydrophobicity, TBARS, and TVB-N. After six days of storage at 4°C, significant differences emerged between F and E versus CK, but SI remained similar to CK. At the end of storage, new protein bands emerged in group E, and circular dichroism analysis showed that the decrease ratio of α-helix content in these groups was higher compared to CK. In short, shrimp muscle pretreated with SI exhibited superior integrity, with less damage and better quality during storage. PRACTICAL APPLICATIONS: Pretreatment before shelling can improve shelling efficiency. Our results demonstrate that slurry ice treatment causes less damage to shrimp muscle. Furthermore, storage experiments confirmed that this treatment does not promote deterioration during storage. These findings provide theoretical knowledge to support the selection of appropriate processing methods in shrimp production.

Uranium disequilibrium in groundwater downgradient of the Bayan Obo rare earth tailings, Northwest China.

First estimation of the clinical utility of boronotyrosine as a boron delivery compound for boron neutron capture therapy in head and neck cancer.

Study on the detection method of Brucella differential type PCR.

We aimed to quantify inter- and intra-patient variability in serum perampanel concentrations and assess whether concentrations predict efficacy or tolerability. We conducted a retrospective cohort study of 68 children and adolescents (< 18 years) treated at the Danish Epilepsy Centre (2017-2024), analysing 311 TDM samples. Dose-normalized concentration ratio was summarized as the concentration-to-dose-per-kilogram ratio (C:(D/kg)) and evaluated by age group and co-medication category: enzyme-inducing anti-seizure medications (ASMs), valproate or non-inducing ASMs. Clinical outcomes were change in seizure burden, seizure freedom and adverse effects. Perampanel concentrations were outside the recommended therapeutic range in 13.8% of samples, and C:(D/kg) varied 59.2-fold across patients. Children < 6 years had lower concentration than adolescents > 12 years, and enzyme-inducing ASMs markedly reduced C:(D/kg). Overall, 80.9% of patients had reduced seizure burden, and 20.6% became seizure-free, but serum concentrations did not correlate with seizure freedom or adverse effects. TDM is valuable for detecting under- or over-dosing caused by age-related clearance changes or enzyme-inducing co-medications. While dose adjustments can be guided by serum concentrations, optimization should ultimately target clinical seizure reduction and tolerability.

Abstract. Rubisco is the central photosynthetic enzyme that catalyzes the fixation of CO2 to RuBP, initiating the most dominant carbon assimilation pathway on Earth that supports nearly all trophic chains in the biosphere. The CO2 fixation reaction expresses a strong kinetic isotope effect, producing biomass depleted in 13C and leaving characteristic imprints in sediments and sedimentary rocks, which are widely used to reconstruct past biological activity and environmental conditions, including ancient atmospheric CO2 levels. Despite its importance, carbon isotope fractionation of Rubisco (ϵRubisco) has been measured in only a limited number of organisms, with most studies focusing on land plants rather than on major contributors to the sedimentary record, such as cyanobacteria and coccolithophores. This scarcity reflects the complexity of existing experimental procedures and the high cost of instrumentation. Here, we present a simplified method that overcomes these limitations, eliminating the need for complex purification protocols, specialized equipment, and experimental designs that yield little CO2 fixation and high uncertainties. We use a simplified purification procedure yielding semi-purified Rubisco extracts, together with an Apollo–Picarro δ13C-DIC analyzer capable of simultaneously measuring DIC concentration and 13C isotope ratios. Using this protocol, we accurately determined ϵRubisco for the model plant Spinacia oleracea, the cyanobacterium Synechococcus sp., and provide the first determination for the coccolithophore Gephyrocapsa oceanica. The measured values span a striking range, from 13.1 ‰ to 30 ‰, highlighting both the variability of Rubisco fractionation and the versatility of our approach for studying carbon isotope discrimination across diverse biological systems. This study establishes a method that enables reliable determination of ϵRubisco across phylogenetically diverse groups, thereby supports research that provides new insights into the mechanisms of Rubisco fractionation, and improves interpretation of environmental carbon isotope records.

Objectives Amantadine (AMD) is an antiviral and antiparkinsonian drug with a narrow therapeutic window and a recognized risk of severe intoxication. Interpretation of postmortem drug concentrations is complicated by postmortem redistribution (PMR), yet systematic toxicokinetic and multi-tissue PMR data for amantadine remain limited. Methods An integrated investigation of amantadine toxicokinetics and postmortem redistribution was conducted in male rats. For toxicokinetic assessment, a single oral dose of 450 mg/kg (LD50) was administered, and concentrations were quantified in blood and nine tissues over a 96-h period. For the PMR study, rats received low (42 mg/kg), medium (LD50), and high (2 × LD50) doses, followed by controlled postmortem storage at 4 °C and 20 °C for up to 96 h. Amantadine concentrations were determined using validated HPLC–MS/MS methods and analyzed by pharmacokinetic and statistical approaches. Results Amantadine was rapidly absorbed and widely distributed, exhibiting pronounced tissue-specific heterogeneity. The liver and kidney showed the highest exposure, whereas accumulation in the brain and testis was limited. Postmortem redistribution was substantial and tissue dependent, and was strongly influenced by dose, postmortem interval, and storage temperature. Blood concentrations were unstable over time, while solid organs, particularly the liver and spleen, exhibited higher and more sustained postmortem concentrations. Notably, selected inter-tissue concentration ratios (e.g., liver-to-lower limb muscle and spleen-to-brain) displayed consistent, dose-dependent trends across postmortem conditions. Conclusions This study provides a comprehensive characterization of amantadine toxicokinetics and postmortem redistribution across multiple biological matrices. The findings underscore the limitations of relying solely on postmortem blood concentrations and support the complementary use of selected tissues and inter-tissue concentration ratios as comparative indicators in toxicological interpretation. These results offer mechanistic insight into postmortem drug dynamics and provide practical reference data to improve the interpretation of suspected amantadine intoxication.

I-/I3 --based thermocells show great potential for low-grade heat harvesting because of their affordability, adjustable electrochemical Seebeck coefficient (Se), and ease of device integration. However, current strategies of developing high-performance I-/I3 --based thermocells usually result in substantial imbalance between Se and ultimate output power due to deteriorated ion transportation and replenishment. Herein, we propose a novel fluoride-mediated coordination strategy to break this trade-off. By introducing potassium fluoride and 1-(2-hydroxyethyl)imidazole (HEI) into the electrolyte, we engineer in situ formation of thermosensitive HEI-I2F- coordinated complexes. These complexes undergo reversible temperature-dependent precipitation and dissociation, creating a significant concentration ratio gradient, thereby remarkably increasing Se. Concurrently, the introduced ligand ions disrupt the original hydrogen bonding of water molecules, facilitating superior ion transport for increased outputcurrent. Consequently, the optimized thermocell achieves a high Se of 1.53mVK-1 and a maximum power density of 124.74mWm-2 at ΔT=30K. This work provides a versatile and effective pathway toward high-power thermocells for low-grade heat harvesting.

In order to establish a rapid and sensitive LAMP visual detection method for Cherry Virus A on-site, this study used the conserved fragment of the CVA coat protein (CP) sequence as a template for primer design. The rapid visual LAMP detection method for Cherry Virus A was successfully established by optimizing the reaction system components (concentration ratio of internal and external primers, and concentrations of loop primers, Bst DNA, Mg2+, dNTPs and betaine) and reaction conditions (temperature and time). This method enables specific detection of Cherry Virus A and facilitates visual inspection of crude nucleic acid extracts within 40 min, significantly reducing the diagnostic turnaround time. The limit of detection is 67.54 pg μL−1 (cDNA), which is 100 times more sensitive than PCR. Analysis of 70 field sweet cherry samples revealed an RT-LAMP positivity rate of 91.42%, significantly surpassing the 71.42% achieved by RT-PCR. This method is suitable for the rapid on-site detection of Cherry Virus, and can also provide a theoretical reference for the early diagnosis of cherry viral diseases.

Infections caused by Staphylococcus aureus remain a global health problem, particularly due to increasing antibiotic resistance that limits the effectiveness of conventional therapy. This condition encourages the development of alternative antibacterial agents based on natural materials. Bidara leaves (Ziziphus mauritiana) and betel leaves (Piper betle L.) are known to have antibacterial activity, however the potential of their combination against Staphylococcus aureus has not been widely studied. This study aims to evaluate the antibacterial activity of a combination of ethanol extracts of bidara leaves and betel leaves against the growth of Staphylococcus aureus with three variations of concentration ratios, namely 100%:0%, 50%:50%, and 0%:100%. There are also 2 control groups, namely a positive control using the antibiotic Clindamycin and a negative control using 10% DMSO. The study used a true experimental design with a post-test only control group design and was conducted using an inhibition zone test with the disc diffusion method. In addition, phytochemical screening tests were carried out to identify active compounds in each extract. The results of phytochemical screening of bidara leaf extract, betel leaf extract, and their combination showed positive results containing secondary metabolites in the form of alkaloids, flavonoids, tannins, terpenoids, and phenols. The results showed that the average diameter of the inhibition zones formed were group 1 (100%:0%) 25.6 mm, group 2 (50%:50%) 19.4 mm, and group 3 (0%:100%) 26.2 mm. The Mann-Whitney test showed significant differences between groups (P=0.000), however further tests showed that there were no significant differences between the treatment groups. In conclusion, the combination of bidara leaf (Ziziphus mauritiana) and betel leaf (Piper betle L.) extracts has antibacterial activity against Staphylococcus aureus, but does not show a synergistic effect and is not more effective than single extracts.

Abstract Dibutyl phosphate (DBP) is a problematic compound in reprocessing plants, affecting not only the extraction processes of U and Pu, but also the vitrification of high-level liquid waste (HLLW). Previous full-scale glass melter tests indicated that even a minor amount of DBP in simulated HLLW altered the cold-cap morphology, making it larger and thicker. In this study, small-scale melter tests revealed that the influence of DBP on cold-cap morphology is related to the Zr/Mo concentration ratio in HLLW. When the Zr/Mo ratio was high, a tall wall composed of calcined waste components formed around the cold cap, and a thick waste layer developed at its bottom. These DBP-induced changes were mitigated by lowering the Zr/Mo ratio; the cold cap then adopted a flatter morphology similar to that observed in the absence of DBP. Graphical abstract

ABSTRACT Photovoltaic‐thermal (PVT) solar collectors offer a promising solution for the co‐generation of electricity and heat. Here, we investigate a spectral‐splitting PVT collector that integrates a selectively‐absorptive hybrid liquid‐solid optical filter (LSOF). The LSOF offers a stable and efficient alternative to conventional nanofluid‐based optical filters for spectral‐splitting PVT collectors. Two photovoltaic (PV) configurations are examined—a silicon (Si) solar cell operated under non‐concentrated sunlight, and a gallium arsenide (GaAs) solar cell operated under concentrated sunlight. A Fresnel lens with a geometric concentration ratio of 100 is employed to focus sunlight onto the LSOF, which selectively absorbs ultraviolet and sub‐bandgap infrared radiation for heat generation. The remaining solar spectrum is transmitted to the PV cells for electricity generation. This configuration enables fluid temperatures of up to 86.8°C, while maintaining the PV cell temperature as low as 38.2°C, demonstrating effective thermal decoupling between the PV and solar thermal absorber. The PV cells have electrical efficiencies of 7.9% for the Si cell and 5.7% for the GaAs cell. Although the efficiency and output heat temperature of the current LSOF‐based PVT collectors remain modest owing to optical losses and elevated temperatures, the system demonstrates the potential of hybrid optical filtering for solar co‐generation.

Cariprazine, a third-generation antipsychotic, is indicated for schizophrenia and bipolar I disorder. Affordable formulations are essential for improving access and adherence, particularly in resource-limited settings. We aimed to assess the bioequivalence, safety, and tolerability of a newly developed generic hard capsule Vocarzine (1.5 mg) compared to a branded reference product of cariprazine hard capsule (Reagila®) under fasting conditions in healthy adult participants. In a randomized, open-label, single-dose, two-period, two-sequence crossover design, 30 healthy male and female participants received a single oral dose of either the test or reference product, with 4-week washout period. Pharmacokinetics were evaluated using validated LC-MS/MS methods. Bioequivalence was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of peak plasma concentration (Cmax) and area under the concentration-time curve from time zero to 72 h (AUC0-72h) fell within 80-125%. Twenty-nine participants completed the study. The GMR (90% CI) for Cmax was 91.92% (85.07-99.33%) and for AUC0-72h was 92.85% (88.86-97.02%), both within the bioequivalence acceptance range (80-125%). Both formulations were well tolerated; mild nausea was the most common adverse event, and no serious adverse events were reported. The two hard capsule formulations were bioequivalent, in terms of rate and extent of absorption, with a comparable safety profile, supporting the use of vocarzine as a safe, effective, and potentially cost-saving alternative. Clinical trial number: The ClinicalTrials.gov registration number is NCT07121868, retrospectively registered on August 13, 2025.

Follicle-stimulating hormone (FSH) plays a pivotal role in reproductive physiology and is increasingly recognized for its involvement in the extragonadal system. The biological activity of FSH, which is modulated by glycosylation, varies with age, reproductive status, and pathological conditions. Although the serum FSH immunoreactive concentrations are measured routinely for patients with reproductive disorders, the significance of assessing the biological activity of FSH remains unclear. In this study, we aimed to develop a novel, rapid, and animal-free assay to quantify FSH bioactive concentrations using HEK293 cells co-expressing the human FSH receptor (FSHR) and a cyclic adenosine monophosphate biosensor. The assay demonstrated high specificity, reproducibility, and linearity, with minimal cross-reactivity with structurally related hormones. Application to clinical serum samples from postmenopausal women revealed a strong correlation between FSH immunoreactive and bioactive concentrations. Notably, estrogen replacement therapy resulted in a significant reduction in both FSH immunoreactive and bioactive concentrations, as well as in the FSH bioactive -to-immunoreactive concentration ratio, suggesting that FSH glycosylation patterns may have been altered, leading to a decrease in its bioactive concentrations. The findings collectively suggested that assessing FSH bioactive concentrations, in addition to immunoreactive concentrations, may provide further insights into hormonal regulation and its relevance to therapeutic evaluation. The biosensor-based assay could offer a practical and efficient tool for advancing our understanding of FSH function in both reproductive and non-reproductive contexts.