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Parkinson's disease (PD) is characterized by progressive loss of nigral dopaminergic neurons, resulting in disabling motor symptoms. Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD. Here we report the 12-month primary safety end point and interim efficacy outcomes from a phase 1/2, open-label, multicenter trial evaluating STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. Eight individuals with moderate PD underwent bilateral intraputaminal transplantation at two escalating doses (n = 4 per cohort), followed by 12 months of immunosuppression. Seven participants completed 12-month follow-up; one participant died from a pulmonary infection. No serious adverse events were attributed to the cell product, no graft-induced dyskinesias were observed and serial magnetic resonance imaging showed no evidence of tumor formation. These findings support the feasibility and favorable safety profile of human pluripotent stem cell-derived dopaminergic progenitor transplantation in this early-phase study, with risks primarily associated with the immunosuppression regimen. Ongoing follow-up to 36 months will further evaluate durability, clinical outcomes and graft function. ClinicalTrials.gov identifier: NCT05635409 .

Microbial communities serve as vital indicators of ecosystem health and play a crucial role in facilitating the restoration of degraded soil ecosystems, acting as key participants in soil nutrient cycling. However, the interaction mechanisms between microbial communities and plants in different soil zones under varying restoration approaches remain unclear. This study focused on a restoration area of a decommissioned open-pit coal mine in an alpine region, comparing the microbial community structure and nutrient characteristics of rhizosphere and bulk soils under two restoration methods: herbaceous vegetation restoration and sea-buckthorn shrub restoration. The aim is to reveal the impact of different restoration measures on the soil-microorganism interactions. The results demonstrated that soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), total potassium (TK), and available potassium (AK) contents were significantly higher in the herbaceous restoration area (O) than in the seabuckthorn area (S), by 51.7%, 88.6%, 38.2%, 13.1%, and 4.7%, respectively. Compared to bulk soil, rhizosphere soil exhibited higher microbial community diversity and richness. Furthermore, seabuckthorn rhizosphere microbial diversity surpassed that of herbaceous rhizosphere. Different restoration areas (DRE) significantly (p&#x2009;<&#x2009;0.05) influenced the relative abundances of Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria. The seabuckthorn area showed higher proportions of Proteobacteria (26.48&#x2009;-&#x2009;42.86%) and Actinobacteria (28.26&#x2009;-&#x2009;45.19%) compared to the herbaceous area. Functional gene prediction revealed that the seabuckthorn area expressed significantly higher abundances of core metabolic functional genes related to energy production and conversion (C), amino acid transport and metabolism (E), carbohydrate metabolism (G), and lipid metabolism (I) than the herbaceous area. Additionally, a symbiotic functional guild comprising animal pathogens, endophytes, lichen parasites, plant pathogens, and wood saprotrophs was formed in the seabuckthorn area. Redundancy analysis (RDA) indicated significant positive correlations (p&#x2009;<&#x2009;0.05) between Acidobacteria, Chloroflexi, Actinobacteria, and Ascomycota and the contents of SOC, TN, and total phosphorus (TP). Bacterial networks formed with Actinobacteria as the core hub, comprising 300 edges connecting 50 nodes, while fungal networks were dominated by Ascomycota. Based on these findings, this study proposes a synergistic restoration strategy characterized by "herbaceous-induced short-term priming" coupled with "seabuckthorn-driven long-term stability." This strategy provides a theoretical foundation for the targeted microbial regulation of ecological restoration in mining areas.

We sought to determine whether the endoscopic grade of gastric atrophy (according to Kimura-Takemoto) affects the likelihood of successful first-line H. pylori eradication. We conducted a retrospective analysis of consecutive patients hospitalized at Wuhan Fourth Hospital between November 2021 and November 2025. Eligible individuals had a positive urea breath test confirming H. pylori infection, were diagnosed with chronic atrophic gastritis via gastroscopy, received a bismuth-containing quadruple regimen as first-line therapy, and returned for a follow-up breath test at least 4 weeks post-treatment. Prior to therapy (within 28 days), each patient underwent high-definition white-light gastroscopy. Two independent endoscopists, unaware of patient allocation, retrospectively reviewed all images to grade atrophy using the Kimura-Takemoto system. Patients were assigned to either the closed-type (C-type) or open-type (O-type) atrophy group. The primary endpoint was eradication failure, defined as a positive follow-up breath test. Logistic regression (univariate and multivariate) was used to identify factors independently linked to treatment failure. A total of 154 patients completed follow-up and were included. The overall eradication rate was 76.6% (118/154). In the open-type atrophy group (n = 26), the eradication rate was only 42.3% (11/26), significantly lower than the 83.6% (107/128) observed in the closed-type group (P < 0.001). After adjusting for confounders such as body weight and age, multivariate analysis revealed that endoscopic open-type atrophy was independently associated with eradication failure (OR = 8.287, 95% CI: 3.150-21.804, P < 0.001). The extent of endoscopic gastric mucosal atrophy independently predicts a lower efficacy of first-line H. pylori eradication. For patients with Kimura-Takemoto open-type atrophy, clarithromycin-containing quadruple regimens should be used cautiously. Alternative clarithromycin-free regimens (e.g., tetracycline-, metronidazole-, or levofloxacin-based therapies, or high-dose amoxicillin with PPI/vonoprazan) or susceptibility-guided individualized therapy are recommended in clinical practice.

Psychosis prevention relies on early detection of individuals at clinical high risk for psychosis (CHR-P). The effectiveness of the CHR-P state is constrained, in part, due to clinical assessments requiring specialist interpretation of narrative interviews, limiting scalability. Here, we evaluate whether large language models (LLMs; deep learning models trained on large text corpora to process and generate language) can extract clinically meaningful information from such interviews to support psychosis risk assessment. We assessed 11 open-weight LLMs on 678 partial PSYCHS interview transcripts from 373 participants (77.7% CHR-P). Models inferred CHR-P status and estimated severity and frequency across 15 symptom domains, benchmarked against researcher-rated scores. Larger models achieved the strongest classification performance (Llama-3.3-70B: accuracy = 0.80, sensitivity = 0.93, specificity = 0.58). LLM-generated symptom scores showed good correlations with researcher-rated scores (ICCsev = 0.74, ICCfreq = 0.75). Performance disparities were minimal across most demographic groups but varied across sites. Generated summaries were largely faithful to source transcripts, with low rates of clinically relevant confabulation (3%). Errors primarily reflected over-pathologisation of non-clinical experiences. While accuracy scaled with model size, smaller models achieved competitive performance with substantially lower computational cost. These findings demonstrate that open-weight LLMs have the potential to assess psychosis risk from psychometric interview transcripts, supporting scalable, human-in-the-loop approaches to early detection.

Foslevodopa/foscarbidopa continuous subcutaneous infusion (LDp/CDp CSI) has emerged as an effective and well-tolerated therapy for reducing OFF and increasing non-troublesome ON in advanced Parkinson's disease (PD). Neuropsychiatric adverse events (AEs) have been reported in both clinical trials and real-world studies, with some real-world cohorts suggesting higher rates among patients with prior hallucinations or cognitive impairment. The present study aimed to determine the incidence and risk factors of neuropsychiatric AEs in a large prospective real-world cohort. We analyzed data from the DATs-PD GETM Spanish Registry, an observational, prospective, multicenter, open-label study. 214 patients treated with LDp/CDp CSI were included. Median age was 69&#x2009;years, and median disease duration was 12&#x2009;years. At baseline, 35% had cognitive impairment, 25.7% hallucinations/psychosis, and 26.2% impulse control disorders (ICDs). During follow-up after initiation (median 163&#x2009;days), 19.2% developed at least one neuropsychiatric AE, mostly mild-moderate, and only 2.3% required device removal. Most events occurred more than 1&#x2009;month after treatment initiation. In adjusted Cox, none of the evaluated variables were associated with the development of hallucinations/psychosis/confusion. The presence of ICD at baseline was associated with an increased risk of ICD-related AEs. Neuropsychiatric AEs, mainly hallucinations/psychosis, occurred in a clinically relevant proportion of patients treated with LDp/CDp CSI. However, they were generally mild-to-moderate and rarely led to treatment discontinuation. Except for ICD, baseline cognitive and psychotic features were not associated with higher incidence. These findings support its use in appropriately selected patients while highlighting the importance of individualized careful clinical monitoring.

Micro/nanoplastics are quietly infiltrating human bodies through dietary intake, water consumption, and dermal exposure. Here, we assessed the interaction of nanoplastics (NPs) with &#x3b2;-amyloid (A&#x3b2;), helping to understand the likely mechanisms of NPs accumulation in brain and potential impacts on Alzheimer's disease (AD). SH-SY5Y cells served as an in vitro model of AD and were treated with fluorescently labeled NPs (NPf). In in vivo study, 5XFAD mice were fed with environmentally relevant doses of NPf for two weeks, and mouse behavior was analyzed by open field test. Brain tissue sections combined with confocal microscopy enabled the quantification and spatial localization of NPf in the brain. NPs aggregated with A&#x3b2; fibers and formed micrometer-sized agglomerates. In AD cell models, these agglomerates increased the intracellular NPs accumulation, reactive oxygen species formation and ethoxyresorufin-O-deethylase activity, ultimately inhibiting neurite outgrowth and causing cell death. In the AD mice, NPs exposure worsened the mice disease-related behaviors (e.g., reduced movement distance and speed) and resulted in larger NPs agglomerates and highly co-localization with A&#x3b2; in brain, consistent with the in vitro results. This study provided important data on NPs interaction with A&#x3b2; fiber from ex vivo to in vivo models, helping to understand the mechanisms of NPs accumulation in the brain.

In a first-in-human trial (NI006-101), the monoclonal antibody cliramitug, targeting misfolded transthyretin, demonstrated a favorable safety profile and time- and dose-dependent reductions in surrogate markers of cardiac amyloid burden over the course of 12 months in patients with amyloid transthyretin cardiomyopathy (ATTR-CM). Here we evaluate the long-term safety and efficacy of cliramitug in a subgroup of participants of the NI006-101 trial who continued treatment in a second open-label extension (OLE2) and further explore dose- and time-dependent effects on amyloid depletion, cardiac biomarkers and cardiac structure and function. Twenty-three participants (20 receiving background treatment with tafamidis, all male) entered OLE2 and received a median of 10 additional infusions, increasing the maximum total exposure to 24 infusions and extending the median follow-up to 29.3 months. Thirteen participants initially treated with &#x2264;10&#x2009;mg kg-1 were up-titrated to 30&#x2009;mg kg-1 during OLE2. Treatment adherence was high (98%), with no treatment-related serious adverse events or discontinuations. Continued treatment and up-titration in participants with lower prior exposure led to further reductions in cardiac extracellular volume on MRI and tracer uptake on bisphosphonate scintigraphy. Improvements were also observed in NT-proBNP and troponin T levels, left ventricular relaxation, filling pressures and wall thickness. Increases in Kansas City Cardiomyopathy Questionnaire scores suggested potential quality-of-life benefits. Consistent with results from the original trial, cliramitug showed favorable long-term safety and further reductions in cardiac amyloid burden following up-titration to 30&#x2009;mg kg-1. These time- and dose-dependent improvements across structural, functional and biomarker endpoints support the therapeutic potential of amyloid-depleting therapy with cliramitug in ATTR-CM. ClinicalTrials.gov: NCT04360434 .

The effects of surface functionalization and metal ordering on the structural, mechanical, and electrochemical properties of two-dimensional transition metal carbide MXenes remain insufficiently understood, particularly for double-metal systems. Nb2TaC2 and Ta2NbC2 monolayers, in bare and oxygen-functionalized forms, are studied using density functional theory to determine how these factors affect lithium adsorption, diffusion, and storage performance. Oxygen functionalization increases in-plane stiffness (Young's modulus up to 384.7 N/m) and stabilizes Poisson's ratios, while lithium preferentially adsorbs at metallic sites on bare MXenes and at carbon sites on O-functionalized surfaces, with adsorption energies reaching -3.70 eV. Nudged elastic band calculations show that oxygen functionalization slightly increases diffusion barriers, from 0.05 to 0.21 eV for Nb2TaC2 and from 0.06 to 0.24 eV for Ta2NbC2, while fast Li-ion mobility is maintained. Open-circuit voltage analysis indicates average voltages of 0.74 to 0.95 V with capacities up to 412 mAh/g. These results provide design guidelines for tuning surface chemistry and metal ordering in double-metal MXene anodes for Li-ion batteries.

Background/Objectives: Type 2 diabetes is a group of metabolic disorders whose pathophysiological outcome is sustained hyperglycemia. Several medications are available for the treatment. SGLT2 simultaneously inhibits glucose and sodium reabsorption in the renal proximal tubule, resulting in urinary glucose excretion. This study assessed the pharmacokinetic profiles of two empagliflozin 25 mg drug products under fasting conditions in healthy Mexican subjects to establish bioequivalence. Methods: This was a randomized, open-label, two-way crossover, single-dose, prospective study with a 7-day washout period. Eligible subjects were healthy adult Mexican volunteers. The drugs were dosed orally, according to the randomization, after 10 h of fasting and 4 h before breakfast, with 250 mL of 10% glucose solution at room temperature. Serial blood samples were collected before and after dosing. Empagliflozin concentrations were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Results: A total of 32 subjects were enrolled, and 30 completed the study. Pharmacokinetic parameters Cmax, tmax, AUC0-t, AUC 0-&#x221e;, and t&#xbd; of empagliflozin for test and reference formulation, expressed as mean &#xb1; SD, were 578.28 &#xb1; 125.60 ng/mL, 2.72 &#xb1; 0.85 h, 4370.88 &#xb1; 769.50 ngh/mL, 4423.93 &#xb1; 776.02 ngh/mL, 7.62 &#xb1; 0.83 h, and 593.99 &#xb1; 156.78 ng/mL, 2.86 &#xb1; 1.00 h, 4313.24 &#xb1; 885.02 ngh/mL, 4368.04 &#xb1; 887.75 ngh/mL, and 7.61 &#xb1; 0.68 h, respectively. The 90% CI for Cmax, AUC0-t, and AUC 0-&#x221e; were 98.30 [92.72-104.22], 101.72 [98.77-104.77], and 101.64 [98.73-104.63], respectively. Serious adverse events were not observed. Conclusions: Our study demonstrated bioequivalence between the empagliflozin formulations tested in healthy subjects under fasting conditions.

The discovery of moir&#xe9; superlattices has introduced a new dimension to twist engineering, enabling structure-level modulation beyond conventional compositional design. However, the electrochemical energy-storage properties of MXene moir&#xe9; superlattices remain largely unexplored. In this work, we systematically investigate structural stability, electronic band structures, mechanical moduli, and some key electrochemical energy storage properties for representative bilayer Ti3C2O3 moir&#xe9; superlattices with different twist angles (0&#xb0;, 21.78&#xb0;, 27.8&#xb0; and 38.22&#xb0;) and interlayer stacking structures (AA-, AB- and AC-stackings) using first-principles calculations. All investigated moir&#xe9; superlattices are predicted to have negative binding energies with respect to the Ti3C2O2 monolayer and also show high mechanical stiffness (690-723 N m-1 for Young's modulus and 265-286 N m-1 for shear modulus) with Poisson's ratios about 0.27-0.29. The bilayer superlattices retain metallic electronic band dispersions and the robust mechanical integrity with limited in-plane lattice variation (<1.6%) and moderate interlayer expansion (<0.5 &#xc5;) upon Li intercalation, indicating excellent structural stability during charge-discharge cycles. The moir&#xe9; modulation introduces diverse adsorption sites and enhances Li accommodation, leading to high theoretical capacities (300 mAh g-1) and favorable average open-circuit voltages (1.7 V). Meanwhile, the relatively low migration barrier (<0.2 eV) is also obtainable for Li ions in Ti3C2O2 moir&#xe9; superlattices, suggesting promising rate performance. Notably, the adsorption energy landscape of Li species in the interlayer spacing of bilayer Ti3C2O2 superlattices is mainly modulated by the local atomic registries of moir&#xe9; spots, while the adsorption energies on the surfaces of bilayer structures are determined by the surface O-terminations and the intercalated Li layer in the interlayer spacing. Overall, our current work highlights the tuning of the electrochemical properties of MXenes through twist engineering, probably offering a new theoretical paradigm to further optimize the performance of moir&#xe9; superlattices as electrode materials in lithium ion batteries.

MXenes are a rapidly expanding family of two-dimensional transition-metal carbides, nitrides, and carbonitrides whose physicochemical behavior in aqueous and biological environments is dominated by their surface terminations (e.g., -O, -OH, and -F), rendering them intrinsically active solid-liquid interfaces. These terminations regulate interfacial charge distribution, hydration structure, adsorption equilibria, and colloidal stability, positioning MXenes as dynamic interfacial systems rather than passive nanomaterials. Rational control of surface termination chemistry therefore represents a central strategy for governing MXene interactions with electrolytes, proteins, and biological media. This review provides a comprehensive and critical analysis of recent advances in MXene surface-termination engineering from the perspective of interfacial and colloidal science, with emphasis on etching routes, post-synthetic modification, dimensional tailoring (2D, 3D, and emerging 4D architectures), and characterization approaches relevant to interfacial behavior. We examine how termination chemistry controls key interfacial properties, including zeta potential, dispersion stability in physiological electrolytes, hydration-mediated wetting, and protein corona formation, and how these interfacial factors collectively shape biological responses such as cytotoxicity, inflammatory signaling, antibacterial activity, and reactive oxygen species generation. Particular attention is devoted to termination-driven charge regulation and coordination chemistry at solid-liquid interfaces, which govern adsorption-desorption dynamics, molecular loading, and stimulus-responsive release, as well as the modulation of optical and magnetic responses. By critically comparing reported systems and explicitly addressing unresolved challenges related to termination heterogeneity, interfacial aging, and scalability, this review clarifies structure-interface-function relationships that underpin MXene performance in complex environments. Finally, we identify emerging strategies and open questions for designing surface-terminated MXenes with predictable and controllable interfacial behavior, highlighting their broader relevance as model systems for dynamic solid-liquid interfaces with bio-functional implications.

Pelvic examination is a core clinical skill in undergraduate medical education, requiring integration of technical competence with communication, consent and patient-centred care. Despite its importance, opportunities to learn pelvic examination are variable, and educational approaches differ widely. Existing reviews have largely focused on short-term learner outcomes rather than broader questions of implementation, cultural context and patient impact. This review aimed to map teaching methods used to teach pelvic examination, examine how effectiveness is defined and evaluated, and identify reported barriers and enablers to implementation. A scoping review was conducted in accordance with Arksey and O'Malley's framework and prospectively registered with Open Science Framework. Database searches were undertaken in June 2024 and repeated in May 2026. Studies describing pelvic examination teaching for undergraduate medical students were included. Data were extracted and analysed using inductive qualitative content analysis. Outcomes were mapped to the Kirkpatrick model to enable comparison. Fifty-five studies were included. Teaching approaches were grouped into received knowledge (e.g., lectures, videos and e-learning) and experiential approaches (e.g., models, professional patients and clinical encounters). Most studies combined multiple modalities. Evaluation predominantly focused on learner-centred outcomes at Kirkpatrick levels 1 and 2, particularly confidence and perceived competence. No studies assessed behavioural change or patient-level outcomes. Implementation was influenced by resource availability, workforce pressures, organisational culture and equity considerations. Pelvic examination education requires balanced, feasible and culturally sensitive approaches that extend beyond short-term learner outcomes. Future research should prioritise patient perspectives, long-term behavioural change, inclusivity and cost-effective implementation within real-world clinical contexts.

This debate addresses the choice of placebo versus active comparator in randomized controlled trials (RCTs) for chronic migraine (CM), a disabling condition with high global burden. Placebo-controlled designs have traditionally been considered the gold standard for new treatments, allowing quantification of placebo and pharmacological effects, ensuring internal validity, smaller sample sizes, and regulatory acceptance. Yet, ethical concerns arise from the possibility that participants may be denied effective treatments. The emergence of migraine-specific therapies targeting the calcitonin gene-related peptide (CGRP) pathway has prompted calls for active comparator designs. Such trials may enhance clinical relevance, support recruitment, and better mirror clinical practice compared with placebo-controlled RCTs. However, defining a universal standard of care may be challenging given global disparities in access, cost, and treatment preferences, limiting the feasibility of RCTs with active comparators. Placebo-controlled trials remain valuable, but alternative strategies, including short placebo phases with open-label extensions, add-on designs, or three-arm trials (investigational treatment, placebo, active comparator) may reconcile scientific rigor with ethical considerations. Ultimately, the optimal trial design depends on the research question, regulatory requirements, and evolving definitions of standard care in CM prevention.

Floods pose significant risks to groundwater quality, particularly for households relying on private wells. This study investigates the vulnerability of private wells completed in fractured crystalline bedrock aquifers in a small watershed near Quebec City (Canada), to surface water intrusion and microbiological contamination during and after flood events. The study hypothesis was that flood events promote these processes in vulnerable private wells, with contrasting responses between non-floodplain and floodplain settings. Thirteen wells and three surface water sites were monitored over 1.5&#xa0;years, encompassing four flood events. A novel multi-indicator approach was applied, combining hydrostatic and barometric pressure monitoring, stable isotopic composition of water (&#x3b4;18O, &#x3b4;2H), partial pressure of CO2 (pCO2), pH, and microbiological indicators (total coliforms, Escherichia coli), to characterize flood-related contamination dynamics in private wells before, during, and after flood events. Results show that nearly all wells were contaminated by bacteria, with concentrations peaking during the 14-day post-flood period. Surprisingly, non-floodplain wells exhibited higher and more episodic contamination than floodplain wells, likely due to their location in recharge zones favoring vertical intrusion of stormwater. In contrast, floodplain wells displayed more constant but moderate contamination, possibly reflecting a hydraulic connection with the river. Stable isotope peaks confirmed rapid intrusion of surface water in several wells after summer storms, whereas the spring flood showed isotopic similarity between recharge water and groundwater, indicating that stable isotopes were not a reliable tracer of spring flood intrusion under snowmelt conditions. Hydrostatic data revealed sharp piezometric peaks indicative of focused recharge pathways, while pCO2 and pH analyses distinguished open versus closed geochemical system conditions, providing further insight into the vulnerability of the wells. Collectively, these findings highlight diverse contamination pathways and emphasize persistent vulnerability of private wells beyond immediate flood events. This study underscores the importance of proactive monitoring and improved well management to better assess and safeguard private well drinking water quality under increasing hydro-climatic variability.

There is an unmet need for effective, off-the-shelf therapies for relapsed or refractory aggressive B&#x2009;cell non-Hodgkin lymphoma (B-NHL). Part&#x2009;2 of the current study was an open-label, nonrandomized, phase&#x2009;1 study of escalating doses of the CD19-4-1BBL co-stimulatory molecule, englumafusp alfa, in combination with glofitamab in patients with relapsed or refractory B-NHL. Obinutuzumab pretreatment was administered 7&#x2009;days before the first glofitamab dose. Glofitamab step-up dosing in cycle 1 was followed by 11 cycles of glofitamab plus englumafusp alfa. Englumafusp alfa was administered at escalating doses, with the initial dose on cycle 2 day&#x2009;8 (C2D8) or cycle 1 day&#x2009;10 (C1D10). Primary objectives were to establish the maximum tolerated dose, and safety and tolerability. A total of 134 patients were enrolled, including 109 with aggressive B-NHL and 25 with indolent B-NHL. The maximum tolerated dose of englumafusp alfa was not reached; one dose-limiting toxicity occurred (grade&#x2009;5 Pneumocystis jirovecii pneumonia). Adverse events were reported in 98.5% of all patients, with grade&#x2009;3/4 adverse events in 59.0%. Grade&#x2009;5 adverse events occurred in ten patients. In the subgroup of C2D8 patients with aggressive B-NHL (n&#x2009;=&#x2009;83), overall response and complete metabolic response rates were 68.7% and 56.6%, respectively; among those without previous exposure to chimeric antigen receptor T&#x2009;cell therapy (n&#x2009;=&#x2009;41), the corresponding rates were 73.2% and 65.9%. Pharmacodynamic changes following englumafusp alfa administration supported its co-stimulatory mode of action. These data demonstrate that the addition of englumafusp alfa to glofitamab is associated with encouraging efficacy and robust pharmacodynamic modulation, as well as a safety profile consistent with glofitamab monotherapy, in patients with relapsed or refractory B-NHL. CTIS identifier: 2022-502616-37-00 ; ClinicalTrials.gov identifier: NCT04077723 .

The increasing use of antibiotics in livestock farming raises concerns about environmental impacts. This study examined the effects of three commonly used veterinary antibiotics - Tylosin, Enrofloxacin, and Oxytetracycline - on manure greenhouse gas (GHG) emissions and fertilizer quality during solid manure storage. Aliquots of fresh cattle manure (10&#x202f;kg) were either spiked with high or low concentrations of each antibiotic, or left untreated as Control, then incubated in open buckets for 110 days to simulate manure heaping. Emissions of CO2, CH4, and N2O were measured using a static chamber with a laser spectrometer. Tylosin (High and Low) treatments and High-dose Enrofloxacin significantly increased manure N2O emissions (2.1&#x202f;&#xb1;&#x202f;0.2 to 2.5&#x202f;&#xb1;&#x202f;0.4&#x202f;%), exceeding the IPCC default values of 1&#x202f;% manure-N. All antibiotic treatments increased CH4 emission factors (6.4&#x202f;&#xb1;&#x202f;0.7 to 14.2&#x202f;&#xb1;&#x202f;1.1&#x202f;g CH4 kg-1 VS) compared to the Control (2.2&#x202f;&#xb1;&#x202f;0.5&#x202f;g CH4 kg-1 VS) and the IPCC default value (4.44&#x202f;g CH4 kg-1 VS). Overall, antibiotic residues increased the global warming potential (GWP) of stored solid manure by 218&#x202f;% compared to the Control. Despite the slightly greater nitrogen losses from increased N2O emissions, the final fertilizer quality of the manure remained unaffected by the antibiotic treatments. Besides health concerns related to antimicrobial resistance, our findings on environmental impacts call for a One Health approach to promote sustainable antibiotic use in livestock production.

To describe the epidemiological characteristics of children and young people presenting to the emergency department (ED) with acute severe behavioural disturbance (ASBD) who were deemed to require oral sedative medication. Secondary analysis of a randomised controlled open-label multi-centre trial of oral olanzapine versus oral diazepam for the management of ASBD in children and young people aged nine to 17&#x2009;years for whom epidemiological data were recorded. There were 348 participants enrolled in the randomised controlled trial (RCT). The majority were female (215/348, 62%) with a mean age of 14.6&#x2009;years (standard deviation 2.2). The most common pre-existing medical or mental health condition was anxiety (122/299, 35%) followed by attention deficit hyperactivity disorder and autism spectrum disorder (33% and 32%, respectively). Two-thirds of the study population (216/348, 62%) had previously attended the ED for ASBD management and 61% (212/348) reported previous intentional self-harm. Nearly three-quarters (247/348, 71%) were accessing psychiatric care in the community prior to their ED presentation. Half of the study population (178/348, 52%) presented to the ED with emergency services (e.g., ambulance, police). The median length of stay in the ED was 5.7&#x2009;h (interquartile range 3.9-10.2&#x2009;h) and 28% (98/348) of study participants required admission to hospital. For children and young people presenting to the ED with ASBD who were deemed to require oral sedative medication to assist with behavioural containment, pre-existing mental health disorders were common. There is a need for focussed management procedures for more targeted, trauma-focussed care for children and young people presenting to the ED with ASBD and for support and education in the pre-hospital setting. The primary study (PEAChY-O) was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12621001236886) prior to commencement.

Aqueous zinc-ion batteries (AZIBs) possess distinct benefits in cost and safety, but bilateral interfacial failures on Zn anodes and MnO2 cathodes constrain their practical applications. Inspired by zymogen-to-enzyme activation, this work proposes a biomimetic, intelligent electrolyte additive strategy that enables on-demand protection on both electrodes. This strategy employs an inert additive, 1,4-butane sultone (BS), which preferentially adsorbs on the electrode surfaces. Upon water attack and localized pH increase, BS can be activated, generating open-ring derivatives (OBS) to facilitate the in situ construction of bilateral protective interphases with organic-inorganic composite components. Concurrently, it optimizes Zn2+ solvation structures to lower the desolvation energy barrier. Residual BS further traps SO4 2- and H2O and sustains the OBS formation for preventing interfacial alkalization. Consequently, the BS-modified Zn//Zn cell delivers a lifespan exceeding 4000&#xa0;h, and the Zn//Cu cell attains an ultrahigh initial Coulombic efficiency of 97.62%. Zn//MnO2 full cells maintain capacity retention of 92.7% and 80.5% after 100 cycles at 0.2 A g-1 and 8000 cycles at 6 A g-1, respectively. Such a strategy not only delivers a high-performance electrolyte additive for AZIBs but also offers biomimetic inspiration for the development of electrolytes in other metal-based battery systems.

Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available &#x3b1;-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN3/AcOH/Et3N system at its highly reactive &#x3b1;-methylene-&#x3b3;-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene-heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 &#xb5;g/mL conc.), C. krusei (up to 51% inhibition at 10 &#xb5;g/mL conc.) and C. albicans (up to 52% inhibition at 10 &#xb5;g/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents.