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Polymer blends are an industrially important class of materials with numerous applications in coatings, electronics, packaging, automotive, and medical materials. Many desirable material properties can be obtained from the proper control of blend morphology and processing, necessitating in-depth studies relating processing, structure, and properties of these materials. Here, we study the mixing and processing of a polymer system consisting of high-density polyethylene (HDPE) and cyclic olefin copolymer (COC) using atomic force microscopy (AFM) in combination with Raman spectroscopy and optical microscopy. Phase separation is observed, even at COC concentrations as low as 5%. The morphology of the phase separation can be described as a droplet-matrix of COC in HDPE, combined with a co-continuous blend morphology at higher concentrations (12%) of COC. In this system, the topography combined with mechanical property data from AFM provides unambiguous images of the phase separation while co-localized Raman spectroscopy provides complementary chemical identification. This work provides a methodology to obtain an informative physical and chemical picture of the phase separation in this polymer system both before and after processing which can contribute to the improved design, processing, and quality control of industrial polymer blends.

Bacterial peptidoglycan fragments (PGNs) are pathogen-associated molecular patterns that activate the mammalian innate immune system, particularly through NOD2 signaling pathways. Since NOD2 is a cytosolic sensor in mammalian cells, cellular assays are commonly used to identify bioactive PGNs that elicit NOD2 response, with muramyl dipeptide (MDP) long recognized as the minimal NOD2 agonist. However, recent studies have highlighted the intracellular phosphorylation of MDP by mammalian N-acetylglucosamine kinase (NAGK) as a critical prerequisite for NOD2 activation, emphasizing the need for further investigation into other host-mediated processing of PGNs. In this study, we examined how various bacterial PGNs, differing in saccharide and stem peptide length, undergo intracellular structural modifications within mammalian cells. Our findings show that disaccharide PGNs are processed through intracellular glycosidic cleavage to generate monosaccharide MurNAc-containing PGNs intracellularly, followed by NAGK-dependent phosphorylation, uncovering an additional essential step that precedes NOD2 activation. To identify the glycosidase responsible for disaccharide PGN cleavage, we provide biochemical and cellular observations that human O-GlcNAcase functions as a promiscuous glycosidase capable of processing certain disaccharide PGNs and potentially modulate their NOD2 activation. Furthermore, we demonstrate that PGNs with a lysine-type tripeptide stem are specifically cleaved into dipeptides and that phosphorylated PGNs are subjected to dephosphorylation in mammalian cells. Together, these findings offer insights into the metabolism and intracellular processing of PGNs in mammalian cells, which are crucial in shaping the host innate immune responses.

The aim of this study was to evaluate scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDS) as complementary analytical tools for supporting continuous improvement in pharmaceutical granule manufacturing. Pilot-scale cefixime granules for oral suspension were prepared as defined process scenarios, including placebo, reference, intermediate, stress-exposed, and optimised batches. SEM was used to compare granule morphology, surface integrity, and agglomeration behaviour, whereas EDS provided qualitative and semi-quantitative information on localised elemental composition, with emphasis on sulfur as an API-related marker and oxygen-to--sulfur trends as surface-sensitive indicators of process- or stress-related variability. Intermediate and stress-exposed batches showed increased surface roughness, microstructural deterioration, and higher oxygen-to-sulfur ratios, whereas reference and optimised batches showed more uniform morphology and comparable elemental profiles. The findings indicate that SEM/EDS can provide useful material-level insight into process-related variability and may support root--cause investigation and process refinement. Overall, SEM/EDS is proposed as a complementary, localised, and semi-quantitative approach for supporting continuous improvement in pharmaceutical granule manufacturing.

Locator devices are increasingly being used to help manage wandering among people living with dementia. While these technologies can be beneficial, they also raise significant ethical questions. These ethical questions are faced in both the development and use of these devices. The aim of this study is to develop and present a question-based ethical framework that can guide both the use and the development of locator devices in dementia care, ensuring that stakeholder needs and values are balanced effectively. A four-step process informed the framework's creation: (1) literature collection (systematic searches of empirical, normative, and development-focused research were conducted); (2) content analysis (an inductive qualitative analysis of collected literature identified key ethical concerns, arguments, and stakeholder perspectives); (3) iterative framework drafting (insights were translated into open-ended questions and refined through regular team discussions); and (4) stakeholder consultation (feedback from health professionals, older adults, family members, developers, and ethicists was used to refine and finalize the framework). The resulting framework is organized around 3 themes-vision, process, and impact-each containing guiding questions that encourage dialogical reflection and decision-making. For "use," these questions help care communities clarify goals, define processes, and assess outcomes. For "development," they aid developers in articulating device objectives, anticipating risks, and aligning product features with end-user values. By providing guiding questions that can be adapted to local needs and contexts, this framework fosters a more inclusive, transparent, and ethically accountable approach to developing and using locator devices in dementia care.

The exponential growth of biomedical data hinders the rapid adoption of evidence-based practices in the Military Health System. This is critical in austere environments where teams rely on limited resources. Generative artificial intelligence (AI) offers a potential solution for rapidly synthesizing evidence. This comparative study evaluated the utility and feasibility of generative AI tools compared to human clinical experts in identifying protocols for surgical instrument reprocessing in austere settings. We conducted a descriptive comparative study to query four AI platforms (NIPRGPT, ChatGPT, Google Gemini, GenAI.mil) and two clinical experts. The authors prompted each group to identify a single best recommendation for reprocessing surgical instruments in austere environments without steam sterilization capabilities. We compared the outputs based on time-to-completion, accessibility behind Department of War (DoW) firewalls, and clinical validity against a literature review. AI platforms generated recommendations in under 10 minutes. Clinical experts required 14 hours to review and synthesize data. Regarding accessibility, commercial platforms (ChatGPT, Gemini) were blocked by DoD firewalls, while GenAI.mil was accessible. Clinical experts recommended chlorine dioxide (ClO2) due to its sporicidal properties, which ensure sterility assurance. Only ChatGPT matched this recommendation. Conversely, GenAI.mil and Gemini recommended ortho-phthalaldehyde (OPA), and NIPRGPT recommended glutaraldehyde. The AI models prioritized processing speed over sterility assurance. Generative AI significantly reduces the cognitive load and time required to synthesize clinical protocols. However, government-hosted AI tools prioritized logistical factors over safety standards in this study. We identified an accessibility-accuracy paradox where the most accessible tool provided less rigorous safety recommendations. Implementation requires human verification and specific governance to ensure AI supports rather than replaces clinical judgment.

For patients with cancer who experience treatment-related symptoms, emergency department (ED) visits to manage symptoms may occur frequently, contributing to long wait times, unplanned hospital admissions, and possible interruptions in cancer treatment. Studies estimate that 20%-60% of ED visits among patients receiving cancer treatment could be managed outside the ED or hospital setting. Oncology urgent care clinics, created to manage nonemergent conditions in an outpatient setting, are an increasingly recognized solution. The University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center (SCCC) consistently noted difficulty accommodating same-day appointments for patients experiencing acute symptoms, often leading to ED referrals. In response, SCCC developed a same-day appointment option for patients experiencing acute medical concerns: Simmons Acute Care (SAC). The goal was to address nonemergent acute issues, thereby reducing avoidable ED visits and improving the quality of care. Early planning with a multidisciplinary team focused on identifying factors that contributed to ED visits, with these findings serving as the core of SAC planning. A pilot study was implemented to evaluate the feasibility and identify the challenges for SCCC patients who were receiving any cancer treatment modality, or who had completed treatment within the past 90 days. Conditions appropriate for outpatient management were identified through a literature review and assessment of the U.S. Centers for Medicare and Medicaid Services definition of potentially preventable ED visit diagnoses. Nine clinical pathways were developed to provide evidence-based care. A fast-track laboratory courier system and expedited imaging were incorporated into the process model. A dashboard to identify clinical outcomes, process measures, and trends was created to track real-time data and provide monthly updates to core staff. The dashboard tracked key metrics while maintaining engagement and identifying needs for additional resources. Notably, current data reflect that 75%-80% of SAC encounters are seen and discharged home with a next-day follow-up call by a registered nurse. Approximately 15% of the SAC encounters are directly admitted to the hospital, bypassing the ED. These data reflect a response to the evolving complexity of cancer care and patient care needs by offering a rapid connection to an experienced care team. SAC is now the standard pathway for oncology patients who meet the criteria.

Environmental contamination by synthetic dyes and toxic heavy metals from textile effluents has emerged as a serious global concern. This study evaluates untreated Hippophae rhamnoides sea buckthorn leaf biomass (SBLB) as a low-cost biosorbent for the simultaneous removal of Methylene Blue (MB), Congo Red dye (CRD), and hexavalent chromium [Cr(VI)] from aqueous solutions. Batch adsorption experiments were conducted by varying pH (2-10), adsorbent dosage (0-6 g L-1), contact time (5-240 min), and initial concentration. Optimal adsorption was achieved at pH 5-6 with a dosage of 2 g L-1, reaching equilibrium at 180 min for MB and CRD and 120 min for Cr(VI). Maximum adsorption capacities (qₘ) were 78.74 mg g-1 (MB), 45.45 mg g-1 (CRD), and 106.38 mg g-1 (Cr(VI)), while experimental equilibrium capacities (qₑ) were ∼35.7, 39.8, and 32.8 mg g-1, respectively. Kinetic data followed the pseudo-second-order model (R2 > 0.99), and equilibrium behavior was best described by Freundlich isotherm, indicating heterogeneous multilayer adsorption. Thermodynamic analysis confirmed a spontaneous and mildly endothermic process. Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM) analyses confirmed the role of surface functional groups and morphology in adsorption, highlighting SBLB as an efficient, low-cost biosorbent for contaminants removal. The present study is novel in its direct utilization of untreated Hippophae rhamnoides (sea buckthorn) leaf biomass as a low-cost and sustainable biosorbent, eliminating the need for chemical activation or energy-intensive modification processes. It uniquely demonstrates the simultaneous removal of structurally diverse pollutants, including cationic dye (Methylene Blue), anionic dye (Congo Red), and toxic heavy metal Cr(VI), within a single adsorption system. A comprehensive investigation integrating kinetic, isotherm, thermodynamic, and surface characterization analyses provides a detailed understanding of the adsorption mechanisms and surface interactions. Furthermore, the study highlights the valorization of an underutilized Himalayan agro-waste, offering a region-specific and environmentally friendly solution for textile wastewater treatment with practical applicability.

LIKE-HETEROCHROMATIN PROTEIN 1 (LHP1) is a polycomb group protein that exists in shared multiprotein complexes that harbor core PRC1 and PRC2 proteins. We previously characterized LHP1 in the moss Physcomitrium patens and showed that its function is closely linked with regulation of RNA metabolic processes and the protein is distributed in the nucleoplasm, subnuclear foci, and the nucleolus. To gain mechanistic insight into PpLHP1-mediated gene regulation, in the present study genome-wide changes in transcript profiles of genes affected by loss-of-PpLHP1 function were studied using pplhp1 mutants. RNA-seq analysis reveals a key role for PpLHP1 in regulating energy metabolic processes, ribosome-related pathways, stress signaling/responsive pathways, DNA transcription, etc. ChIP using H3K27me3 coupled with qRT-PCR shows that PpLHP1 suppresses transcription at 5S rRNA promoters and the untimely activation of genes regulating developmental transition by PRC2-dependent and independent mechanisms. To study how PpLHP1 finds its targets in different nuclear compartments and the roles of the multiple NLSs and the conserved domains in guiding the protein, FRAP and deletion studies were performed. These show that PpLHP1 is a mobile protein that diffuses freely in the nucleoplasmic space showing different retention times in the nucleolus, nucleoplasm, and the subnuclear foci indicating its differential affinity for targets at these sites. Expression of PpLHP1 fragments in protonema cells and its subsequent visualization under confocal microscope shows that localization of PpLHP1 to different subnuclear compartments is guided by the monopartite NLS2, CD, and CSD that also play a key role in promoting subnuclear foci formation in the nucleoplasm.

Modern municipal wastewater treatment plants (WWTPs) effectively reduce contaminants of emerging concern in treated effluents, including rare earth elements (REEs). However, REEs preferentially accumulate in sludge, raising concerns regarding downstream sludge processing and biosolids utilization while presenting opportunities for resource recovery. This study presents a proof-of-concept for REE decontamination of biosolids while partially preserving the biosolid matrix through room-temperature acid leaching. Dewatered digestate biosolids collected from WWTP in southern Wisconsin were subjected to acid leaching under various operating conditions to evaluate REE extraction and matrix preservation. The optimal protocol consisted of leaching with 2 M hydrochloric acid at a biosolid-to-leachant ratio of 0.2 kg L-1 for a single 0.5 h cycle at room temperature in batch operation. Under these conditions, 144 mg kg-1 of total REEs were recovered, corresponding to 80 ± 4% recovery of the pseudo-total REEs, while resulting in a biosolid mass loss of 37 ± 4%. The protocol maintained comparable performance following a 50-fold scale-up and when applied to biosolids collected from WWTP in northern Illinois, demonstrating process adaptability. Fourier transform infrared spectroscopy (FTIR) and elemental analysis indicated that key polysaccharide components of the biosolid matrix were preserved following acid treatment, although partial denaturation and solubilization of protein and nucleic acid fractions likely occurred. Energy-dispersive X-ray spectroscopy (EDX) showed the persistence of phosphorus, sulfur, magnesium, calcium, manganese, iron, and other micronutrients in the residual biosolids. These findings demonstrate an ambient-temperature, infrastructure-compatible strategy that simultaneously enables REE removal, resource recovery, and partial preservation of a potentially-reusable biosolid matrix, providing a foundation for future circular-economy approaches to municipal biosolids management.

Chinese hamster ovary (CHO) cells are widely used for the production of recombinant biologics, but their application in transient gene expression (TGE) systems remains limited by reduced efficiency at high cell density, known as the cell density effect (CDE). Increasing evidence suggests that extracellular factors, including extracellular vesicles (EVs), contribute to this limitation. However, their role in CHO-based TGE systems remains poorly understood. In this study, we investigated the impact of EV accumulation and depletion on transfection efficiency, virus-like particle (VLP) production, and cellular responses in CHO cells. EV production increased approximately 4.2-fold at high cell density and was influenced by extracellular conditions, including media replacement. EV depletion partially restored transfection efficiency and productivity to approximately ∼60% of low cell density levels. In addition, moderate overexpression of UDP-glucose ceramide glucosyltransferase (UGCG) further enhanced transfection efficiency and VLP productivity, reaching levels comparable to low cell density conditions when combined with fresh media replacement. Transcriptomic and proteomic analyses showed that EV depletion induces a multi-layered cellular response, including transient activation of proteostasis pathways, sustained upregulation of vesicle trafficking, and later activation of lysosomal and autophagy-related processes. These responses suggest that EV removal perturbs extracellular homeostasis and triggers adaptive intracellular reprogramming. Overall, these findings demonstrate that EVs play a dual role in CHO TGE systems, acting both as inhibitory extracellular components and as regulators of cellular homeostasis. Modulating extracellular conditions in combination with targeted manipulation of lipid metabolism can partially alleviate the CDE but also introduces stress-related trade-offs that must be considered in process design.

El Niño-Southern Oscillation (ENSO), the Earth's dominant mode of interannual climate variability, is closely linked to sea surface temperature (SST) variability in the central and eastern equatorial Pacific. Accurate subseasonal-to-seasonal SST forecasting in this region supports ocean monitoring and environmental assessment. We propose WDFormer (Wave Decomposition Former), a daily SST forecasting model built on a "decomposition, multi-path processing, and adaptive fusion" paradigm. The model uses 365 daily SST observations from local 4×4 grids around representative ENSO monitoring stations to predict daily SST values over 7-90-day horizons. WDFormer first applies wavelet decomposition to separate the input sequence into a smoother low-frequency component and a higher-frequency residual. Lightweight MLP-based branches process the original and low-frequency components, while a Transformer-based branch models the residual dynamics. Outputs are integrated through a learnable gating mechanism. Experiments on daily OISST data from five representative ENSO subregions show that WDFormer outperforms several deep learning baselines at most 30-90-day horizons. Comparisons with persistence and daily climatology confirm that persistence dominates at very short lead times, whereas WDFormer provides clearer advantages as the horizon extends. An ONI-based ENSO-phase and El Niño-stage stratified evaluation shows that WDFormer achieves the lowest RMSE under El Niño, La Niña, and Neutral conditions, as well as during El Niño onset/development, mature/peak, and decay/termination stages for the 90-day task. Bootstrap confidence intervals and paired RMSE comparisons further support the robustness of the 90-day results. These results support decomposition-based heterogeneous modeling for daily SST forecasting at 30-90-day horizons and motivate broader extensions to probabilistic and multi-variable forecasting.

Microbial transglutaminase (mTG) is a frequently used processed food additive, and the consumption of its cross-linked complexes is rapidly expanding. Despite numerous reports concerning its public safety, it is designated as a processing aid and classified as safe for use. mTG and/or its cross-linked complexes can compromise human health. They represent non-self peptides, resulting in non-immune-tolerable neoepitopes. They are proinflammatory, allergenic, immunogenic, pathogenic, human immune system suppressors, and potentially toxic, hence raising concerns for public health. mTG functionally mimics the endogenous transglutaminase and was recently identified as an inducer of celiac disease, potential primary biliary cholangitis, and neurodegenerative diseases. The present review describes the potential mechanisms and risky effects of mTG, highlighting its thermostability and broad pH activity range, its problematic, underregulated, genetically engineered origin, and public health concerns. The national food regulatory authorities are urged to reconsider mTG's status, prioritizing public health protection over the mTG's health-damaging consequences.

There is large variability in speech perception outcomes across cochlear-implant (CI) users. One factor that contributes to this variation is the neural modulation encoding in the periphery, which can vary along the implant electrode array. Since temporal envelope cues are crucial for speech perception with a CI, previous studies have shown that there is potential of deactivating electrodes based on poorer behavioral measures of neural modulation processing to improve speech perception. However, behavioral measures are typically time-consuming and require active feedback from the CI recipient. A potentially useful objective measure of neural modulation processing is the electrically-evoked auditory steady-state response (eASSR). Recently, the across-array variation of eASSRs has been shown to strongly correlate with speech perception in noise in CI users. In the present study, we demonstrate feasibility to measure 40-Hz eASSRs with clinical pulse rates across multiple electrodes. Next, we investigated whether objective electrode-selection based on individual across-array eASSR patterns has the potential to improve speech perception in CI users. 40-Hz eASSRs were recorded across the whole implant electrode array by means of EEG. A custom-built EEG system with a resolution of 262 kHz was used in order to be able to remove CI-stimulation electrical artifacts. Next, the across-array variation of eASSR amplitudes was used as a basis for individualized electrode-selection. Two experimental MAPs with 11 electrodes (MAPs A and B) were created for each participant: MAP A retained electrodes that were considered better at conveying temporal envelope cues, and MAP B those that were considered poorer at it. Speech perception performance with the clinical and the two experimental MAPs was assessed using speech perception tasks in quiet and in noise, and correlated with eASSR pattern metrics after accounting for the effect of tonotopical changes on speech perception due to electrode deactivation. Results showed that MAP A consistently performed better than MAP B in all three listening conditions, but both still perform worse than the clinical MAP. Furthermore, results suggested that higher eASSR amplitudes overall and greater across-array variation were associated with better performance with MAP A, even after controlling for tonotopical effects. No such associations were observed for MAP B. These findings suggest that automatic, objective electrode-selection strategies based on local neural modulation encoding of cochlear regions along the electrode array is useful for individual clinical CI fitting, with the potential to improve speech perception outcomes in CI recipients.

The electrochemical chlorine evolution reaction (CER) serves as the cornerstone of the chlor-alkali industry. Ruthenium dioxide (RuO2)-based materials represent some of the most widely employed electrodes in industrial processes. A mechanistic understanding of reaction processes at the electrode surface is essential for the rational design and targeted modulation of CER kinetics. Herein, we carried out ab initio molecular dynamics (AIMD) simulations with an explicit liquid-solid interface to unravel the CER mechanism on the RuO2(110) surface. Surface phase diagram analysis identifies the oxygen-saturated configuration as the thermodynamically stable surface. Compared with the conventional simulation based on a gas-solid model that largely neglects the explicit solvation effect, the explicit aqueous environment reshapes the reaction energetics. Electrochemical chloride adsorption, namely the Volmer step, is facilitated by lowering the free energy barrier to 0.53 eV, whereas the Heyrovsky step to generate Cl2 is coupled with the desorption of Cl2 from the surface solvent layer, leading to the generation of kinetically unfavorable solvated Cl2. Thus, a more positive potential, namely a larger overpotential, is required to drive the CER. In comparison, there is no barrier for the Heyrovsky step without explicit solvation. This study highlights the importance of incorporating explicit solvation in electrochemical simulations, and provides insights for the design of CER catalysts.