Palladium oxide (PdO) thin films (~ 60 nm thick) were grown on quartz substrates using a two-step process involving DC magnetron sputtering of Pd films followed by thermal oxidation in dry air at 450-750 °C for 4 h. In this work, a systematic temperature-dependent oxidation strategy is employed to directly correlate phase evolution, microstructural transformation, thickness effects, and hydrogen sensing properties of PdO thin films, an aspect that has not been extensively addressed in the existing literature. Structural, morphological, and optical characterizations confirmed full Pd-to-PdO conversion above 550 °C, with crystallite sizes increasing up to 30 nm. AFM and FESEM showed porous, domain-like morphologies, and UV-Vis analysis indicated direct band gaps in the range of 2.06-2.42 eV. XPS verified the presence of stoichiometric PdO with Pd²⁺ oxidation states. Electrical measurements revealed semiconducting behavior with thermally activated conduction, yielding activation energies between 0.045 and 0.092 eV depending on annealing temperature. The sensor response showed no significant dependence on the operating temperature, and the film annealed at 750 °C exhibited the highest sensing response at 400 ppm H₂. The Pt-contacted device detected 1000 ppm H₂ at room temperature, demonstrating stable operation without elevated temperatures. Room-temperature hydrogen sensing tests showed that PdO exhibits two distinct sensing mechanisms: a reversible p-type surface reaction at low H₂ concentrations (≤ 1000 ppm) and a reduction-driven response at high concentrations (2%), where PdO is chemically transformed into metallic Pd, leading to a sharp resistance drop and metallic-like conduction. Beyond temperature variation, PdO thin films with thicknesses of 5, 10, and 20 nm were also fabricated and annealed at 650 °C to examine the influence of film thickness on hydrogen sensing performance.

Autoimmune diseases exhibit active and remission phases. Tissues may retain an 'inflammatory memory', increasing relapse risk after stopping treatment, necessitating ongoing therapy following remission induction. Understanding inflammatory memory and remission-to-recurrence transitions could guide strategies for achieving lasting remission while minimising long-term medication use and costs. Integrative approaches may address autoimmune conditions' multifaceted pathophysiology. Literature suggests utilising modern medicine in ultra-diluted form, with chemotherapy drugs like methotrexate undergoing ultra-dilution. However, extreme dilutions may increase toxicity due to nanoparticles' larger surface area. This study evaluated methotrexate's toxicity at 12c and 30c dilutions. An acute toxicity study evaluated single-dose effects of methotrexate 12c and 30c (2000 μL/kg) in female mice over 14 days, per OECD 423 guidelines. A repeated dose study investigated the impacts of methotrexate 12c and 30c (200 μL/kg) on male and female mice, following OECD 407 protocol. Mortality, clinical signs, body weight, haematology, biochemistry, and histopathology were comprehensively assessed. The acute toxicity study showed no animal fatalities with methotrexate, indicating the median lethal dose exceeded 2000 μL/kg. In the subacute study, methotrexate at 12c and 30c caused no mortality, adverse effects, or abnormal weight changes. Evaluations of haematological parameters, biochemical markers, and histopathological analyses of vital organs revealed no abnormalities. The research study indicates that the oral administration of methotrexate at 12c and 30c to mice over an extended duration, with a dosage of 200 μL/kg, did not exhibit any signs of toxicity or adverse reactions, thus suggesting a safe profile for these potencies.


Radiotherapy during pregnancy is clinically challenging due to concerns about fetal radiation exposure. Proton therapy (PT) with pencil beam scanning can reduce out-of-field dose compared with photon therapy; however, secondary neutron production requires accurate fetal dosimetry.
Approach:
This study presents the design, material characterization, and computational modeling of two anatomically realistic pregnant anthropomorphic phantoms, MaTORI10 and MaTORI30, representing 10 and 30 weeks of gestation and developed for fetal dose assessment in PT. Candidate materials for lung, soft tissue, and bone-including commercial phantom materials, QA materials, and novel 3D-printed or castable polymers-were evaluated using MCNP 6.2 Monte Carlo simulations and compared with reference pregnant-tissue compositions. Depth-dose distributions, neutron yields, and out-of-field neutron spectra were analyzed to characterize radiological behavior. Suitable materials were implemented in physical phantoms constructed by integrating 3D-printed components and cast bone into an ATOM® female phantom. Pregnancy geometries from the University of Florida pregnant phantom library were merged with ATOM CT and surface scans to generate anatomically realistic models with detector inserts. Voxelized computational versions were generated from CT and surface scans and implemented in TOPAS 3.8. A virtual PT brain irradiation plan (78-116 MeV, 10 cm range SOBP, 5 cm modulation, 3 cm radius), with and without a range shifter (RS), was used to quantify in-field and fetal doses.
Main Results:
Material testing showed substantial variability, primarily driven by differences in hydrogen content and density. Both phantoms were successfully constructed and validated by CT imaging. For MaTORI30, modeled fetal dose was on average 29% higher without RS and 21% higher with RS compared to reference materials; for MaTORI10, increases of 10% and 18% were observed.
Significance:
The MaTORI10 and MaTORI30 phantoms provide the first anatomically detailed, pregnant anthropomorphic phantoms whose tissue-equivalent properties were computationally characterized for fetal dose assessment in PT. These phantoms provide a platform for experimental and Monte Carlo-based assessment of fetal dose, facilitating safer radiotherapy and optimal planning for pregnant patients.&#xD.

Selective COX-2 inhibitors are associated with cardiovascular safety concerns, motivating continued exploration of alternative chemotypes. In this study, we investigated the COX-2 inhibitor activity of a library of alkylaminophenols. This was achieved through single-concentration screens used to prioritize compounds with COX-2 inhibition and acceptable cellular tolerability in THP-1 cells, generation of analogs via positional analog scanning (PAS) and molecular docking studies to guide scaffold optimization. Novel compounds were then synthesized by a green Petasis borono-Mannich protocol. Preliminary structure activity relationships (SAR) and molecular descriptor analysis of our one-shot assays allowed us to observe that indoline and para substituted phenols derivatives showed the most promising inhibitory activity. Compound 35e demonstrated a 23-fold increase in COX-2 potency over its parent compound 35, while simultaneously increasing COX-1/COX-2 selectivity by a factor of 25. In LPS-stimulated THP-1 macrophages, 35e reduced IL-6 and TNF-α release in a concentration-dependent manner, with estimated IC50 values of approximately 35 μM and 42 μM, respectively. These concentrations remained below the cytotoxic IC50 in THP-1 cells (67.9 μM), indicating cytokine modulation under non-cytotoxic conditions. Although cellular activity required higher concentrations than direct enzymatic inhibition (COX-2 IC50 = 8.43 μM), these results support a measurable functional anti-inflammatory phenotype. This work establishes alkylaminophenols as an early-stage COX-2 inhibitory chemotype and identifies 35e as a starting point for further optimization.

PIEZO mechanoreceptors play critical roles in fundamental physiological processes such as proprioception or musculoskeletal biomechanics. However, their complex gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective probing tools. Here, we combine molecular imprinting and magnetic concepts to develop tailor-made nanoswitches enabling wireless targeted actuation of PIEZO1. Two epitopes selected in silico from distinct domains of PIEZO1 were used as templates for synthesizing magnetically responsive molecularly imprinted nanoparticles. These nanoswitches showed sub-nanomolar affinity for their respective epitope and recognized PIEZO1 in endothelial cells, similarly to antibodies. Applying magnetic fields to actuate PIEZO1 through nanoswitches led to increased calcium signaling, Yes-associated protein (YAP) nuclear translocation, and significant changes in the expression of genes related to PIEZO1 activity, implying that they can transduce the stimulus into intracellular signaling effects. Finally, this wireless actuation system proved to be effective in differentially modulating the behavior of mesenchymal stem cells. Remarkably, the selective targeting of each epitope led to contrasting downstream signaling cascades, implying distinct roles for each superstructure domain in the sophisticated function of these channels. Overall, this technology constitutes a promising tool for studying PIEZO-mediated mechanobiology, opening perspectives for harnessing its potential toward therapeutic approaches.

Shellfish restoration and aquaculture are considered as innovative methods to mitigate in-water nutrients in coastal waters. Water quality was examined at two oyster aquaculture farms in Potter (2021-2023) and Pt Judith (2023) Ponds in southern Rhode Island, USA. Twice monthly, on a flooding tide, upstream and downstream positions were established and water quality measures were made using fluorometry sondes and laboratory analysis. Significant differences in chlorophyll a, turbidity, and nutrient concentrations between upstream and downstream positions were identified; however, the differences were not consistently greater upstream or downstream. Percent Chl a removed varied from -74% to 64% at Potter Pond among years and -51% to 29% at Point Judith Pond, indicating a deficit or increase in Chl a concentration downstream as compared to upstream over each sampling period. Chlorophyll a measured inside oyster bags was higher compared to the upstream position at Potter Pond, and results from the upstream, downstream, and within farm productivity experiment in both ponds suggest oyster byproducts may facilitate localized and seasonal phytoplankton production. Natural resource managers should consider that while oyster farms in coastal ponds can provide local water clarity through removal of phytoplankton, benefits may be site specific and seasonal.

Advances in the treatment of hematologic malignancies have significantly improved survival, leading to an increasing burden of cancer therapy-related cardiac dysfunction (CTRCD). Early detection of cardiotoxicity is critical, as conventional measures such as left ventricular ejection fraction often identify myocardial injury only after irreversible damage has occurred. Global longitudinal strain (GLS), derived from speckle-tracking echocardiography, has emerged as a sensitive and reproducible tool for detecting subclinical myocardial dysfunction. This review summarizes the role of GLS in the surveillance of cardiotoxicity in patients with hematologic malignancies. We discuss the pathophysiological basis of chemotherapy-induced myocardial injury, including oxidative stress, mitochondrial dysfunction, and inflammatory mechanisms. Evidence supporting GLS as a predictive and monitoring tool is examined across baseline risk stratification, treatment-related changes, and long-term outcomes. GLS consistently demonstrates earlier detection of myocardial dysfunction compared with left ventricular ejection fraction and provides prognostic value in diverse therapeutic settings, including anthracycline-based chemotherapy, hematopoietic stem cell transplantation, and novel immune-based therapies. The integration of GLS into cardio-oncology practice, particularly in combination with cardiac biomarkers, enhances early detection and risk stratification. Despite limitations such as intervendor variability and lack of standardized thresholds, GLS is increasingly incorporated into guideline-recommended surveillance strategies.

Hematological malignancies are characterized by pronounced metastatic potential associated with the chemokine receptor 4/stromal cell-derived factor-1α (CXCR4/CXCL12) signaling axis, high relapse rates, and a profoundly immunosuppressive tumor microenvironment, all of which severely limit the long-term efficacy of existing therapeutic strategies. Herein, we developed a CXCR4-targeted lipid nanozyme platform (Pt-LNP@E5), in which platinum nanozyme catalytic units and E5 peptide were hierarchically integrated to synergistically achieve metastasis blockade and immune microenvironment remodeling. E5 peptide-mediated CXCR4-specific recognition enabled precise tumor cell accumulation of Pt-LNP@E5 and effectively antagonized CXCR4/CXCL12-driven metastatic signaling, thereby markedly suppressing tumor cell migration and dissemination. Meanwhile, the lipid nanocarrier significantly increased the systemic circulation half-life of the platinum nanozyme and maintained catalytic activity. Within the tumor cell microenvironment, the catalytic system selectively generated reactive oxygen species, which not only induced efficient tumor cell killing but also promoted the transition of the immune microenvironment from an immunosuppressive to an activated state, thereby enhancing antitumor immune responses. These synergistic therapeutic effects were validated in two hematological malignancy models, demonstrating significant tumor growth inhibition, metastasis blockade, and immune microenvironment remodeling. In summary, Pt-LNP@E5 represents a promising strategy for the development of novel platinum-based nanomedicines with broad therapeutic potential.

Excellent dual-phase catalysts with spatially separated oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) sites offer great potential for high-efficiency zinc-air batteries (ZABs). However, weak interactions between interfaces and poor electron transfer severely degrade their activity and stability at industrial current densities. Here, we engineer a unique Fe-Ni bifunctional center by anchoring Ni-OH onto the pyridine N4 atoms of the second shell of COPBTC(Fe) and further reveal the self-reconstruction mechanism of the Fe-N4+4/Ni-OH interfacial structure. Theories reveal that when the Fe-N bond is stretched by 1.57% and the Ni-O bond is compressed by 3.83%, the increase in the state electron density of the Fe-Ni active site reduces the ORR/OER rate-determining step energy barrier. Furthermore, the anchoring dual-phase sites stabilize the metal center and suppress metal dissolution. The self-optimized COPBTC(Fe-Ni)strainOH provides an extremely low voltage gap ΔE = 0.547 V. After 20,000 ORR cycles and 40 h of OER operation at 100 mA cm[-2], it still outperforms the benchmark Pt/C-IrO2. Furthermore, at an industrial current density (100 mA cm[-2]), its ZABs exhibit a 4-fold higher cycling stability than the original structure, providing a new possibility for the practical application of ZABs.