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关键词： GLP-1 medications   Obesity   Shared medical appointment   Telemedicine  

摘要： More than half of U.S. adults are eligible for glucagon-like peptide-1 receptor agonist and multi-target incretin (GLP-1) medications. Obesity guidelines recommend multicomponent intensive lifestyle change programs in conjunction with GLP-1 medications; however, there is limited health system infrastructure for this recommended programming.

关键词： Emergency medical services   Trauma care   Emergency first aid responders, EFAR   Community first responders   Community health   Tier 1 integration  

摘要： Trauma accounts for approximately 4.4 million deaths annually and remains the leading cause of mortality among young adults worldwide. In South Africa, interpersonal violence and road traffic crashes strain already overstretched Emergency Medical Services (EMS). The Emergency First Aid Responder (EFAR) addresses this gap through a community-based Tier 1 prehospital model that delivers early trauma care before formal EMS arrives.

关键词： 1α   25-dihydroxyvitamin D3   Chronic obstructive pulmonary disease   Lipid nanoparticle   Pulmonary administration   Serum Ca2+ concentration  

摘要： Chronic obstructive pulmonary disease (COPD) presents with obstructive ventilation disorders. Because no drugs can regenerate destroyed alveoli, there is an urgent need for new treatments that repair alveolar damage. We previously reported revealed that 1α,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) showed emphysema-improving effects in COPD model mice. However, because 1,25(OH)₂D₃ carries a risk of serious adverse effects such as hypercalcemia, strategies to reduce the risk are needed to allow further dose reduction. To solve this problem and achieve efficient intracellular drug delivery, we focused on SS-cleavable proton-activated lipid-like material O-Phentyl-P4C2 (COATSOME^ⓇSS-OP; hereafter "SS-OP") and helper lipid as the components of lipid nanoparticles. In this study, we investigated intracellular drug delivery, emphysema-improving effect, and reduction of adverse effect risk by 1,25(OH)₂D₃-encapsulated SS-OP lipid nanoparticle (SLPs) prepared using either of two helper lipids: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Only 1,25(OH)₂D₃-encapsulated SLPs prepared using DOPE achieved efficient drug delivery, increased nuclear translocation relative to Free 1,25(OH)₂D₃, and successfully induced lung cell differentiation and improvement of the respiratory function at a lower dose. Moreover, the use of DOPE-based 1,25(OH)₂D₃-encapsulated SLPs, reduced elevated serum Ca²⁺ levels, and these formulations are expected to be a therapeutic candidate for COPD.

关键词： Anticancer potential   Fingerprint visualization   Fluorescence applications   Oxadiazole fluorophores   Security applications   Thermogravimetric analysis  

摘要： Two novel donor–acceptor oxadiazole-based fluorophores, FLO-1 and FLO-2, were designed, synthesized, and systematically investigated as multifunctional materials for forensic and security applications and in silico anticancer evaluation. The photophysical properties were examined using UV–visible absorption and fluorescence spectroscopy in solvents of varying polarity, revealing pronounced intramolecular charge-transfer (ICT) behavior, large Stokes shifts, and solvent-dependent emission tunability. FLO-2 exhibited red-shifted absorption and emission, enhanced solvatochromism, and superior fluorescence performance compared to FLO-1, which was attributed to its stronger donor unit and extended π-conjugation. Theoretical investigations, including density functional theory (DFT), frontier molecular orbital analysis, molecular electrostatic potential (MEP), reduced density gradient (RDG), and electron localization function (ELF) analyses, confirmed the donor–π-acceptor architecture and highlighted the efficient charge separation and electronic delocalization, particularly in FLO-2. Practical applicability was demonstrated through successful latent fingerprint visualization on porous and non-porous surfaces using FLO-1 as well as the development of an FLO-2-based fluorescent security ink that remained invisible under daylight and exhibited strong, stable fluorescence under UV illumination. Thermogravimetric analysis confirmed adequate thermal stability for forensic and security applications. Molecular docking studies against the human topoisomerase IIβ-DNA complex and DNA strands demonstrated favorable binding affinities comparable to those of reference anticancer drugs, indicating potential dual activity as topoisomerase IIβ inhibitors and DNA intercalators.

关键词： La(Fe,Si)13-based alloys   Magnetocaloric effect   Melt-extracted microwires   Short-duration annealing  

摘要： La-Fe-Si-based magnetic refrigeration materials have attracted considerable attention for room-temperature magnetic cooling due to their large magnetic entropy change, low cost, and tunable Curie temperature. However, conventional La(Fe,Si)₁₃-based alloys typically require prolonged annealing lasting several days, significantly limiting production efficiency. In this study, La_1.12Fe_11.6Si_1.4 microwires were successfully fabricated by melt extraction, meeting the requirement for short-duration annealing. The structure, phase composition, and magnetocaloric effect of microwires subjected to different annealing durations (0 h, 5 h, and 10 h) were systematically investigated. The as-extracted microwires exhibited a crystallinity of approximately 30%, primarily consisting of LaFeSi and α-Fe phases, with fine dendritic α-Fe grains embedded within the LaFeSi matrix. After 5 h of annealing, the fraction of magnetic phases increased significantly to 60.7 wt%, and the magnetic phases showed a higher Si content. These microwires exhibited a Curie temperature of 209.8 K and the maximum magnetic entropy change ($-\mathrm{\Delta }{S}_M^{\max }$) of ∼8.71 J·kg⁻¹·K⁻¹ under a 5 T field. When the annealing time was extended to 10 h, the transition temperature increased to 215 K, while the maximum magnetic entropy change slightly decreased to ∼8.46 J·kg⁻¹·K⁻¹. Normalized entropy change curves and critical exponent n analysis indicate predominantly second order magnetic transition behavior. This work demonstrates that melt-extracted microwires can achieve a moderate magnetocaloric response after a reduced annealing duration, providing a material form with potential advantages in heat exchange and regenerator geometry.

关键词： ST elevation myocardial infarction (STEMI)   Mortality   Aortic pressure   Survival analysis   Artificial intelligence  

摘要： ST elevation myocardial infarction (STEMI) is a life-threatening condition, and is associated with significant mortality, especially in patients encountering cardiogenic shock. Accurate risk assessment in this population is essential for improving prognosis through the early identification of patients at increased risk of adverse outcomes following successful revascularization. Our previous work has demonstrated outcome predictive value of the aortic pressure (AP) signal.

关键词： R-P phase Srn+1TinO3n+1   Non-equilibrium molecular dynamics   Thickness   Oxygen vacancy concentration   Thermal conductivity  

摘要：

• •
  Thermal conductivity of R-P phase Sr_n+1Ti_nO_3n+1 increases with thickness (ranging from 5 to 16 nm).
• •
  Sr₂TiO₄ and Sr₃Ti₂O₇ exhibit lower thermal conductivity than SrTiO₃ due to strong phonon scattering at interfaces.
• •
  Oxygen vacancies (0.02%–0.15%) further reduce thermal conductivity at ∼16 nm-thick R-P phase Sr_n+1Ti_nO_3n+1.

关键词： Sulfasalazine   High grade glioma   Glioblastoma   Recurrence   Stereotactic gamma knife radiosurgery   Radiosensitizer  

摘要： Glioblastoma radioresistance is linked to glutathione, a key antioxidant protecting against oxidative stress. Sulfasalazine inhibits the xCT antiporter mediating cystine uptake required for glutathione synthesis in glioma, potentiating radiotherapy in preclinical studies. This trial evaluated safety and therapeutic potential of combining sulfasalazine with stereotactic radiosurgery (SRS) for recurrent glioblastoma. Adults with recurrences were enrolled in a 3 + 3 dose-escalation trial receiving 1.5, 3.0, 4.5, or 6.0 g sulfasalazine orally for 3 days before SRS. Primary endpoint was safety. Secondary endpoints included changes in quality of life (QOL), tumor glutathione-levels, metabolism, and volumes assessed via Functional-Assessment-of-Cancer-Therapy-Brain-questionnaire, glutathione-edited-MR-spectroscopy,¹¹C-Methionine-PET, and MRI. Eleven eligible patients treated with GKRS only due to closed research facilities served as concurrent controls for time to local tumor progression, progression-free survival (PFS), and overall survival (OS). Twelve patients were enrolled and followed until death or consent withdrawal (n = 1). Of 20 adverse events, two were grade 3 (transient lymphocytopenia), four grade 2, and fourteen grade 1. QOL remained stable for 6 months (p = 0.292). Tumor glutathione-levels and metabolic activity were reduced on day 3 (p = 0.010) and 1 month (p = 0.052), respectively. Best RANO-responses were objective (5/11), stable (5/11) or progressive (1/11) for participants vs. stable (2/11) or progressive (9/11) for controls, p = 0.001. Participants had longer local tumor control (median difference: 5.3 months, 95% CI: 1.0-9.6, p < 0.001) and PFS (1.7 months, 95% CI: 0.3-3.0, p = 0.009), with equivalent OS (p = 0.915). In conclusion sulfasalazine and SRS were well tolerated, reducing intratumoral glutathione-levels and associated with more durable local control than SRS alone supporting phase II investigation.

关键词： Analgesia   Drug discovery   Neuropharmacology   Opioid   Sigma-1 receptor   TRPV1   Visceral pain  

摘要： Visceral pain remains a major clinical challenge, often resistant to conventional analgesics. Sigma-1 receptor (σ1R) antagonists enhance opioid antinociception in somatic and neuropathic pain, yet their role in visceral nociception remains unclear. Here we investigated whether σ1R blockade potentiates the antinociceptive effects of µ-opioid agonists in a well-established model of capsaicin-induced visceral pain in mice. To this end, female wild-type (WT) and σ1R-knockout (σ1R-KO) mice received intracolonic capsaicin (0.1%). Visceral pain-related behaviors and referred mechanical hyperalgesia were quantified after subcutaneous administration of morphine, oxycodone, or fentanyl, alone or combined with selective σ1R antagonists (S1RA, NE-100, BD-1063, BD-1047). Opioid specificity was assessed using naloxone, and σ1R dependence using σ1R-KO mice and the σ1R agonist PRE-084. We found that σ1R-KO mice and WT animals treated with σ1R antagonists exhibited reduced spontaneous visceral pain. Morphine, oxycodone, and fentanyl produced dose-dependent inhibition of both pain-related behaviors and referred hyperalgesia. Genetic deletion or pharmacological inhibition of σ1R significantly potentiated these opioid-induced antinociceptive effects, especially at sub-antinociceptive opioid doses. This potentiation was absent in σ1R-KO mice, confirming receptor specificity. Naloxone fully reversed both the antinociceptive effects of all opioids and the potentiation induced by σ1R antagonists, whereas PRE-084 did not modify opioid efficacy. Taken together, these findings demonstrate that genetic deletion or pharmacological inhibition of σ1R significantly enhances µ-opioid–induced antinociception in visceral nociception. This interaction is σ1R-dependent and requires opioid receptor activation. σ1R blockade emerges as a promising adjuvant strategy to improve opioid efficacy against visceral pain while potentially allowing lower opioid doses.