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Care of critically ill patients involves large amounts of medication, perhaps more than any other aspect of the healthcare system. This has substantial environmental impacts. This manuscript describes how the environmental impacts of medications arise along their lifecycle, how to assess those impacts, and opportunities to reduce medication environmental impact across the critical care and caring continuum. Critical care practitioners and trainees have a long career ahead of them, and should be aware of, reflect, and act to address the planetary impact of medications.
Redox-responsive nanomedicine has emerged as a promising approach for site-selective drug delivery by leveraging pathological redox imbalances. Nevertheless, the majority of systems predominantly depend on glutathione (GSH) as a universal trigger, an assumption that frequently fails to account for the complexity and heterogeneity of endogenous redox biology across various diseases. This review critically evaluates redox-responsive nanomedicine beyond GSH, emphasizing emerging endogenous redox triggers such as reactive oxygen species (ROS), thioredoxin systems, NADPH-dependent pathways, hypoxia, and disease-specific oxidative signatures. We discuss advancements in redox-responsive chemistries, logic-gated and multi-trigger nanocarrier designs, and disease-adapted delivery strategies across oncology, inflammatory, metabolic, cardiovascular, and neurodegenerative disorders. Importantly, we analyze translational bottlenecks responsible for bench-to-bedside attrition and propose design principles to enhance biological relevance, safety, and clinical success. By integrating redox biology with nanocarrier engineering, this review outlines a roadmap toward precision redox-responsive drug delivery.
The early and accurate detection of carcinoembryonic antigen (CEA) is critical for cancer diagnosis and prognosis. Herein, we report a novel label-free electrochemical impedimetric immunosensor based on the intrinsic electron-blocking effect of wide bandgap perovskite type BiCoO₃ nanosheets (BiCoO₃ NSs) for the ultrasensitive detection of CEA. The BiCoO₃ NSs were synthesized via a facile hydrothermal method followed by calcination, exhibiting a defined hexagonal flakelike morphology with a large specific surface area for efficient antibody immobilization. Leveraging its wide bandgap (~ 4.2 eV) and n-type semiconducting nature, the BiCoO₃ modified electrode significantly hinders interfacial electron transfer, enabling remarkable signal amplification without the need for noble metal modification. Under optimized conditions, the proposed immunosensor exhibits an ultralow detection limit of 0.01 pg mL⁻¹, a wide linear range (50 fg mL⁻¹ to 1.0 µg mL⁻¹), high sensitivity, and excellent selectivity. The sensor demonstrates satisfactory accuracy in human serum analysis with recoveries exceeding 97%, highlighting its great potential as a reliable and cost effective platform for clinical CEA monitoring and early cancer diagnostics.
Consecutive photoinduced electron transfer (ConPET) has attracted great interest due to its ability to activate inert substrates under mild reaction conditions. The imide-functionalized rylene derivatives are well-documented in the literature as competent chromophores capable of operating via ConPET. Herein, we report the synthesis and characterization of naphthalimide-based organophotocatalyst, JS-2, for CO2 cycloaddition with epoxides to synthesize cyclic carbonates. JS-2 demonstrated remarkable efficiency with just 0.1 mol% catalyst loading at room temperature, atmospheric CO2 pressure, and under visible light irradiation, giving excellent yield and selectivity for a wide range of substrates. Detailed mechanistic investigations and density functional theory calculations confirmed that the reaction proceeds via a sequential two-photon excitation, forming the CO2 radical anion (CO2 •-) as a nucleophile. The heterogeneity and excellent recyclability across five consecutive cycles highlight the robustness and feasibility of the catalyst for practical use. To the best of our knowledge, this is the first report of a completely metal-, halide-, and solvent-free approach, employing a ConPET process and leveraging the nucleophilic reactivity of CO2 •- in epoxide ring opening for a photocatalytic CO2 cycloaddition reaction.
Date fruit is a nutrient-dense and bioactive-rich fruit that has garnered attention for its dual role in athletic performance and sustainable nutrition. Naturally abundant in readily digestible carbohydrates, dietary fiber, essential minerals, vitamins, and polyphenolic compounds, dates provide rapid and sustained energy while supporting glycogen replenishment, oxidative stress mitigation, and metabolic regulation. These functional attributes make dates an ideal candidate for incorporation into sports nutrition products, such as energy bars and functional snacks, offering an alternative to refined carbohydrate supplements and synthetic formulations. The fortification of date-based products with plant proteins, cereals, nuts, seeds, or polyphenol-rich extracts further enhances protein quality, fiber content, antioxidant potential, and micronutrient density without compromising sustainability goals. Moreover, local sourcing, farm engagement, and community-supported agriculture provide educational, cultural, and ecological benefits, fostering mindful dietary behaviors and connecting athletes to their food systems. This review synthesizes recent advances on the chemical composition, functional properties, processing methods, and health-promoting effects of dates, highlighting their strategic potential to support both performance-driven sports nutrition and environmentally responsible diets. Future research should focus on quantifying the environmental impact of date-based functional foods, optimizing formulations for athlete recovery and performance, and translating these findings into practical dietary recommendations.
The growing global plastic waste crisis demands the development of urgent, effective, and sustainable solutions. While conventional recycling methods present intrinsic limitations, microbial biodegradation of plastic waste has emerged as a promising alternative. In this review, we explore the potential of using microorganisms to degrade major hydrocarbon-based plastic polymers and discuss key aspects of this rapidly advancing field, including (i) isolation and characterization of novel microorganisms and enzymes in hydrocarbon-based plastic biodegradation, (ii) development and streamlining of microbial consortia to improve hydrocarbon-based plastic biodegradation efficiency, and (iii) investigation of natural biodegradation processes to illustrate the relationship between plastic degradation and environmental influence. We highlight practical biotechnological approaches and advanced computational tools in hydrocarbon-based plastic degradation, as hydrocarbon-based plastic represents the highest proportion of plastic waste while still lacking effective conversion strategies. Our ultimate goal is to integrate microbial biodegradation strategies into modern waste-management systems and offer a feasible pathway toward a circular bioeconomy, one in which persistent plastic polymers are no longer treated as waste but are converted into renewable feedstocks that support sustainable resource recovery.
The global health workforce faces a projected shortage of more than 11 million health workers by 2030, with the most severe shortfalls in low- and middle-income countries (LMICs). Traditional training models are resource-intensive, rigid, and slow to evolve. These models cannot meet the scale or diversity of workforce needs, nor adapt quickly enough to shifting epidemiology, system demands, or local contexts. Building on previous proposals for shared digital curricula and competency-based ecosystems, this Commentary outlines how the convergence of rapidly growing Open Educational Resources (OER), interoperable digital learning platforms, advances in generative artificial intelligence (AI), and a global governance model creates new opportunities to develop a global, modular, openly licensed curricular ecosystem aligned with regional, national, and global competency frameworks. The authors propose a global initiative to co-create, validate, and disseminate multilingual, adaptable, and competency-aligned training assets across diverse cadres of health workers. Through partnerships among Ministries of Health, academic institutions, professional organizations, and the World Health Organization (WHO), this initiative would strengthen local capacity building, ensure quality and equity, and promote the responsible use of AI in health professions education.
The NIH launched the Rapid Acceleration of Diagnostics (RADx) Initiative to facilitate timely, accurate, and accessible COVID-19 testing, research, and data sharing. The RADx Data Hub (hereafter referred to as Data Hub) is a centralized repository developed to enable secure access and secondary analysis of curated, de-identified data across RADx Initiative programs. Implementing this Data Hub required extensive nested multiteam system collaboration and alignment. Here, we describe the nested multiteam system framework that effectuated data access within a global crisis as a model for future public health challenges. Our work highlights how structured team science methods can enhance the speed and efficacy of data assembly and distribution to accelerate response during public health crises.
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Ocular drug delivery faces tremendous challenges in clinical practice. The eyeball possesses sophisticated anatomical and physiological characteristics that uniquely influence the pharmacokinetics of delivered drugs. This complexity necessitates innovative solutions to ensure effective drug delivery. Conventional ocular drug administration routes (topical, intravitreal, and systemic) each pose unique limitations. With the advancements of biomaterials science and medical engineering technology, nanofiber hydrogels have garnered significant attention, primarily represented by self-assembled peptide-based hydrogels and cellulose nanofiber-based hydrogels. They can be tailored to have precise physical and chemical properties, enabling controlled release of drugs and enhanced biocompatibility. Furthermore, their nanofibrous structure mimics the extracellular matrix, promoting cell adhesion and tissue regeneration. This review introduces advanced manufacturing techniques which are capable of precisely modifying the properties of nanofiber hydrogels to meet specific therapeutic needs. The distinctive advantages of nanofiber hydrogels are elaborated in detail, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. We also delve into the therapeutic applications, potential limitations, and developmental perspectives of nanofiber hydrogels. Preclinical studies have validated their efficacy in treating ophthalmologic conditions such as age-related macular degeneration, bacterial keratitis, ocular alkali burns, and non-infectious uveitis. However, translating these laboratory findings into clinical applications remains limited, primarily due to significant challenges in human trials, including species-specific responses, the complexity of human biology, and the safety of nanofiber hydrogels. Future refinements in fabrication techniques and rigorous safety assessments are necessary to revolutionize the clinical application of nanofiber hydrogels.
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As the US population ages, community-based services (CBS) are critical for supporting older adults' health, independence, and quality of life, yet many remain disconnected from the support for which they are eligible. Following a county-wide older adult needs assessment, this qualitative study used an ecological communication framework and community-based participatory research approach to explore how multilevel communication processes shape awareness, access, and uptake of CBS among adults ages 75 and older. At the individual level, informational gaps, interpretations of fit, and rushed, transactional encounters influenced how CBS messages were noticed, filtered, or dismissed. Microsystem dynamics including shrinking networks, loss of locally situated relationships, and ties built with unfamiliar people in shared spaces shaped the trustworthiness of and access to information. At the exosystem level, organizational communication routines, digital and automated systems, and environmental constraints created opaque and often alienating pathways to services, while community events and outreach at familiar locations provided more relationally grounded opportunities for engagement. Health-care interactions emerged as underutilized opportunities to share CBS information and connect institutional resources and individual needs. Macrosystem narratives emphasizing self-reliance, pride, and earned entitlements contributed to the stigma around help-seeking. Across the levels, peer-to-peer storytelling and informal "information ambassador" roles enacted by trusted local companions emerged as meso-level mechanisms that translated institutional messages into trusted, actionable guidance and bridged gaps between older adults and CBS. Our findings highlight older adults as communicators within complex ecologies of care, foreground location-based storytelling, peer-facilitated access, and community-engaged health care key levers for improving CBS awareness and uptake.
Thrombotic diseases remain a leading cause of global mortality and a significant public health burden. While conventional antiplatelet and anticoagulant therapies are cornerstone strategies, their clinical application is frequently hindered by a significant risk of hemorrhagic complications and limited efficacy in certain patient populations. Consequently, there is an urgent need for safer and more effective antithrombotic agents. Flavonoids, a diverse class of plant-derived polyphenols, have garnered considerable attention due to their potent antiplatelet and antithrombotic activities coupled with a favorable safety profile. This review systematically examines the latest advancements in the therapeutic effects of flavonoids on thromboembolic disorders and elucidates their underlying molecular mechanisms. Evidence suggests that flavonoids function as multi-target inhibitors. They exert antithrombotic effects by regulating platelet activation through interfering with multiple signaling pathways, including the ADP-mediated P2Y1/P2Y12 cascade, cyclic nucleotide (cAMP/cGMP) signaling, and the collagen pathway. Additionally, these compounds inhibit the coagulation cascade by targeting key proteases including thrombin. This review provides an evidence-based roadmap for the development of flavonoid-derived therapies, aiming to facilitate their translation into clinical interventions for the effective management of thrombotic diseases.
Oral administration is favored for its safety, convenience, and cost-effectiveness, yet remains limited by the harsh gastrointestinal environment that often compromises drug stability and efficacy. Plant-derived extracellular vesicles (PDEVs) represent a promising natural platform to overcome this challenge. Exhibiting inherent anti-inflammatory, antioxidant, and anti-tumor properties, PDEVs demonstrate remarkable structural resilience under acidic and enzymatic conditions. Their capacities to cross intestinal barriers, deliver functional microRNAs, and encapsulate poorly bioavailable drugs have shown therapeutic potential in models of intestinal inflammation, metabolic disorders, and gastrointestinal cancers. This review systematically outlines the structural and functional characteristics of PDEVs and evaluates their emerging role as oral carriers for diverse cargoes, including small molecules, nucleic acids, proteins, and probiotics. We also discuss their advantages, design principles, recent advances, current limitations, and future perspectives.
Aqueous zinc-ion batteries (AZIBs) are promising for large-scale energy storage due to environmental friendliness, inherent safety, and low cost. However, the practical deployment of AZIBs is hindered by notorious side reactions at the zinc (Zn) anode, which seriously deteriorate the battery stability and reversibility. Here, we propose guanidine sulfate (GS) as an electrolyte additive, leveraging a cation-anion synergistic mechanism to jointly inhibit side reactions. Both theoretical and experimental results confirm that the guanidine cation (CH6N3 +) preferentially adsorbs on the Zn anode surface, providing an electrostatic shielding effect that promotes uniform Zn deposition. Concurrently, the sulfate anion (SO4 2-) contributes to the formation of a robust solid electrolyte interface (SEI), effectively inhibiting dendrite growth and enhancing interfacial stability. Consequently, Zn||Cu asymmetric cells with GS deliver a high Coulombic efficiency of 99.6% over 1200 cycles, while Zn||Zn symmetric cells exhibit an extended lifespan exceeding 500 h at various current densities. Furthermore, the Zn||Od-NVO·nH2O full cells demonstrate outstanding cycling stability, retaining over 90% of initial capacity after 2000 cycles at current densities of 2 and 5 A g-1. This research provides a viable electrolyte design strategy leveraging cation-anion synergy, offering new insights into electrolyte modulation and advancing the performance of AZIBs.
Effects of secondary coordination regulations for ORR on dual-atom catalysts are clarified over fabricated CoNx + FeNy moieties with P/S-coordination in outer coordination shells of metal atoms, which modulates the electronic asymmetry of dual-metal sites and effectively boosts the ORR catalytic activity.
Soybean (Glycine max) root nodules, formed through symbiosis with nitrogen-fixing rhizobia, are essential for biological nitrogen fixation. While quantifying key nodulation traits, nodule number and weight, is critical for assessing symbiotic efficiency and yield potential, current methods are destructive and labor-intensive, unsuitable for longitudinal monitoring and high-throughput phenotyping. Here, we established hyperspectral leaf reflectance as a non-destructive, high-resolution tool capable of monitoring root nodule development. Using Partial Least Squares Regression models, we connected spectral data with nodule metrics from 528 unique soybean plants across 18 genotypes, inoculated with different rhizobium strains, and under different abiotic stresses. These models achieved high accuracy for predicting nodule number (R2 = 0.75, nRMSE = 6.02%) and moderate accuracy for nodule weight (R2 = 0.53, nRMSE = 12.38%). Crucially, spectral analyses revealed distinct hyperspectral signatures sensitive to nodule traits. While different rhizobium strains induced comparable changes in both nodule traits, and therefore produced highly overlapped spectral domains, diagnostically distinct spectral patterns were generated under drought versus salt stress, with the former suppressing nodulation more significantly than the latter. Furthermore, we demonstrated the effectiveness of our models for real-time in-situ monitoring of nodule development for individual plants. Spectral-nodule trait covariation analyses further revealed leaf signatures correlated with nodule traits primarily through systemic physiological coupling governed by carbon-nitrogen exchange dynamics and plant water status. This study showcased hyperspectral sensing as a transformative methodology, enabling the unprecedented non-destructive quantification of nodulation dynamics, revealing novel physiological insights into plant-microbe-environment interactions, facilitating breeding and management strategies for sustainable soybean production.
RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss the current hurdles to improving AOC efficacy and extending its application, concluding with an outlook on the unique opportunities offered by AOCs beyond traditional oligonucleotides and small-molecule antibody-drug conjugates. We propose that, with focused efforts to overcome key challenges, AOCs have the potential to transform RNA therapeutics, offering treatment options for many previously untreatable diseases.
Harnessing biomass for bio-based industrial biotechnology is vital for addressing global energy needs and mitigating climate change. In this context, microorganisms are the cornerstone of biorefineries based on renewable materials, with applications in bioenergy, agriculture, biomedicine, and other sectors. By engineering metabolic pathways, microorganisms can be tailored to improve yields, tolerate industrial conditions, and selectively produce valuable compounds. Through advances in metabolic engineering and synthetic biology, engineered strains of the yeast Saccharomyces cerevisiae have been successfully developed to efficiently convert the pentose sugars D-xylose and L-arabinose. Despite this important breakthrough, the efficient transport of these sugars remains a major limitation. Sugar sensing and transport in yeast are regulated at both transcriptional and post-translational levels. D-xylose is not recognized as a fermentable carbon source, leading to downregulation of transporter expression, removal from the cytoplasmic membrane, and degradation via ubiquitination in the absence of extracellular glucose. Additionally, transporters exhibit lower affinity for C5 sugars compared to D-glucose, resulting in strong D-glucose repression. To address these challenges, cutting-edge strategies have been successfully employed, including rational protein engineering, directed evolution, and machine learning approaches, to expand the repertoire of C5 transporters available for engineering in S. cerevisiae. Specific D-xylose transporters have been redesigned, with key residues identified to reduce D-glucose affinity, while studies have demonstrated improvements in transporter stability and sugar uptake rates. This review summarizes the key bottlenecks in C5 sugar transport and highlights the major advances and progress made toward creating robust microbial platforms capable of sustainable and efficient bio-based production. This review highlights the progress in understanding and engineering sugar transport systems in Saccharomyces cerevisiae, focusing on transporters for C5 sugars derived from lignocellulosic biomass. It outlines the progression from discovering the first C5 sugar transporters to developing advanced, specialized transporters that improve sugar uptake and utilization. By integrating historical insights with modern strategies, this review showcases how this progress drives the development of yeast platforms optimized for efficient bio-renewable compound production, paving the way for a more sustainable bioeconomy and addressing critical global energy and environmental challenges.