Search Results (1,673)

Anticancer peptides (ACPs) offer a promising alternative to conventional chemotherapy but face challenges, including poor selectivity, limited tumor penetration, low cellular uptake, and rapid degradation in serum. To address these barriers, we developed synthetic mRNAs encoding chimeric ACPs designed for enhanced intracellular delivery and activity. mRNAs for constructs SAK6L9AS(1X), SAK6L9AS(4X), and WTAS-K6L9(4X) were transcribed in vitro and tested against 4T1 breast cancer cells. Cytotoxicity was assessed by cell confluence and MTT assays, while apoptosis was evaluated using caspase 3/7 activation, PI staining, and Annexin V flow cytometry. Our results demonstrate that all SAK6L9AS variants induced robust apoptosis and cellular toxicity in 4T1 cells. Importantly, this work provides the first demonstration of intracellular expression of an mRNA-encoded ACP fused to a cell-penetrating peptide, thereby validating a modular platform for RNA-based delivery of anticancer agents. This study highlights the feasibility of mRNA-encoded peptide therapeutics as a scalable and customizable strategy for cancer treatment. By combining the advantages of mRNA delivery with rational peptide design, ACP chimeras can be expressed directly inside tumor cells, overcoming the limitations of exogenous peptide administration. Our findings support further development of synthetic mRNA therapeutics to generate potent, selective anticancer peptides with reduced systemic toxicity and improved translational potential. Full article

Groundwater contamination caused by dense non-aqueous phase liquid (DNAPL) has long been recognized as a persistent environmental challenge, particularly in fractured porous media. DNAPL migration is highly uncertain due to the heterogeneity and complexity of fracture networks, which complicates risk assessment and remediation design. This paper begins with an overview of mathematical models for multiphase flow migration in fractured media, followed by a systematic analysis and classification of DNAPL migration mechanisms based on laboratory experiments and numerical simulations. Subsequently, key challenges in current DNAPL remediation practices are discussed, including difficulties in monitoring and characterizing fractured aquifers, limited delivery and utilization efficiency of remedial agents, and the back-diffusion of DNAPL from low-permeability zones. Based on this analysis, three primary DNAPL remediation approaches—physical, chemical, and biological methods—are reviewed and evaluated. Finally, future research directions for understanding DNAPL migration and improving remediation strategies in fractured media are proposed. Overall, this review bridges mechanistic knowledge, simulation research, and remediation practice, providing insights that contribute to future technological progress and management decision-making in DNAPL-contaminated fractured aquifers. Full article

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

The agriculture sector plays a pivotal role in global economies, and optimizing its perishable food supply chain (PFSC) is vital to ensuring food security and transparency. The purpose of the study is to develop a blockchain-based smart contract to secure and provide transparency about perishable goods in the PFSC while delivering the goods between the stakeholders, such as farmers, mandis, and wholesalers. The study enhances collaboration between stakeholders by implementing smart contracts. The delivery status and the transactions have been safely recorded and verified by the stakeholder in the PFSC to ensure data integrity all the way through. The blockchain application has reduced fraud and streamlined the flow of goods and information. Moreover, this study emphasizes providing farmers with a straightforward route to the market to empower them. The benefits for the stakeholders are optimizing inventory control and developing appropriate decision-making skills. A three-echelon PFSC can become more resilient and is able to meet changing market demands by implementing blockchain-based smart contracts. Finally, the study employs blockchain technology to establish a decentralized and efficient PFSC, confirming a tamper-resistant system and enhancing stakeholder trust and collaboration. Full article

Background/Objectives: Lipid nanoparticles (LNPs) are a prominent example of delivery systems that are used to prevent the degradation of messenger ribonucleic acid (mRNA) and facilitate cell uptake. Improving LNP transfection efficiency requires careful selection of key formulation components, including the ionizable lipid and the coding sequence of the nucleic acid. Therefore, it is crucial to assess various options for the target cells, as results can differ significantly between cell types. Building on previous work investigating the effect of apolipoprotein E4 on LNP transfection of human monocyte-derived dendritic cells, we assess the impact of different ionizable lipids and compare modifications in the mRNA uridine to further optimize the delivery to these cells. Methods: LNPs containing eGFP mRNA with different uridine modifications were produced via microfluidic mixing and investigated for their in vitro transfection efficiency of human monocyte-derived dendritic cells. Transfection occurred in the presence of apolipoprotein E4 for different encapsulated mRNA concentrations. Delta mean fluorescence intensity and eGFP positive cells were measured by flow cytometry 48 h after transfection. Cell viability was assessed via AnnexinV/7-AAD staining, after comparing this method to LIVE/DEAD^TM Fixable Near-IR staining. Results: This study shows that a combination of SM-102 as the ionizable lipid with eGFP mRNA containing N1-methylpseudouridine enabled the transfection of human monocyte-derived dendritic cells with very high efficiency at low concentrations, allowed for dose sparing, and even led to the LNPs outperforming a specifically tailored electroporation protocol. Conclusions: Improvement of nucleic acid delivery to human monocyte-derived dendritic cells, known for their difficulty to be transfected, was achieved by LNP formulation tuning. Full article

Emergent tracheal intubation in critically ill patients is a common, yet high-risk, intervention. It is frequently complicated by peri-intubation hypoxemia, hemodynamic instability, and metabolic derangements that increase the risk of arrhythmias, hypotension, cardiac arrest, and death. Because the highest-risk interval often occurs in the minutes surrounding induction, when apnea, derecruitment, and abrupt cardiopulmonary shifts converge, oxygenation failure frequently reflects a mismatch between preoxygenation strategy and the underlying physiology rather than inadequate oxygen delivery alone. This review proposes a phenotype-based approach to peri-intubation oxygenation and focuses on four high-risk phenotypes in whom standard preoxygenation strategies commonly fail: obesity, neuromuscular disease, right ventricular dysfunction or pulmonary hypertension, and post-operative respiratory failure with altered respiratory mechanics or airway anatomy. We summarize the key mechanisms that shorten safe apnea time, including reduced functional residual capacity, intrapulmonary shunt, elevated oxygen consumption, rapid derecruitment after induction, and impaired oxygenation–hemodynamics coupling. We then compare preoxygenation modalities as physiologic tools, including facemask oxygen, high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and controlled bag-mask ventilation (BMV), and integrate contemporary randomized trial evidence that informs bedside selection and combination of these approaches. Finally, we synthesize these concepts into a practical, physiology-informed framework to guide clinicians in choosing and troubleshooting preoxygenation strategies in high-risk patients undergoing emergent intubation. Full article

Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in local blood flow that follows neural activity. Many human flicker-light studies report smaller vessel dilation or weaker flow responses in diabetes. This finding can appear even in patients without clear fundus lesions. When NVC is reduced, retinal tissue may receive less oxygen. Lower oxygen delivery can raise oxidative stress and promote inflammation. These changes can then worsen vascular injury. This review describes key NVC pathways and diabetes-related NVU changes in Müller glia, astrocytes, microglia, pericytes, and endothelial cells. The review highlights sympathetic activation as a common stress signal. Pain, anxiety, perioperative stress, and sleep loss can increase sympathetic activity and circulating catecholamines. In the diabetic retina, vascular reserve is often limited. Under these conditions, catecholamines can increase mural cell constriction, reduce nitric oxide (NO)-dependent relaxation, and increase endothelial activation and barrier strain. These effects can shift the baseline state of glial and immune cells and further weaken NVC. The review also summarizes translational tools that can test these links. These tools include heart rate variability, standardized NVC protocols with diameter and flow measures, and retinal organoid and organ-on-a-chip platforms with controlled adrenergic exposure. The review discusses perioperative care packages that reduce stress responses, protect sleep, and manage glucose as practical ways to support retinal microcirculation. More longitudinal human studies are still needed. Retina-specific perioperative endpoints are also needed to clarify causality and to guide intervention trials. Full article

Background: Modern supply chains (SC) are increasingly difficult to manage as they become more complex and interconnected. This encourages companies to rely more on real-time data analysis and analytical tools on operational processes. This study aims to develop and evaluate a Supply Chain Wave Report for a non-food retail that represents goods movement across logistics stages as a continuous analytical flow. Methods: Proposed framework integrates multiple operational phases—Booked Orders, Main Transit, On-Carriage, Warehouse Operations, Store Delivery, and Sales—into a unified monitoring structure. This model can combine operational data with advanced analytics, including Artificial Intelligence-, cloud computing-, and Internet of Things-based technologies. Through cloud-based data infrastructures, System enables data integration and near real-time visibility across organizational functions, allowing continuous monitoring through key performance indicators and predictive simulations. Results: This framework enables dynamic performance of supply chain management and generates real-time signals as goods move across logistics network. This enables managers to detect irregularities earlier and respond before operational deviations propagate further along the chain. Wave-based monitoring approach highlights interdependence between SC stages and illustrates how small disruptions may propagate over time, potentially contributing to effects like bullwhip effect. Conclusions: Findings suggest that a cloud-enabled wave analytics framework can enhance coordination, reduce information gaps, and support informed decision-making in retail. Full article

Broccoli (Brassica oleracea var. italica) is an important crop valued for its nutritional and health-promoting properties, yet its biotechnological improvement is limited by low effectivity and genotype-dependent transformation protocols. The absence of reliable transient expression systems further constrains functional genomics and genome-editing applications. Here, we optimized regeneration and transformation protocols for different broccoli genotypes. Endoreduplication patterns in young tissues were analyzed by flow cytometry to identify suitable explants, and combinations of plant growth regulators were tested to develop an efficient organogenic medium. Stable transformation was achieved via Agrobacterium tumefaciens using nptII and eGFP markers. Cotyledons and hypocotyls up to day 7 showed similar endoreduplication patterns, with abundant 2n cells, but hypocotyls exhibited higher regeneration capacity. The optimized medium supported efficient organogenesis while maintaining diploidy. Transformation efficiency reached 10.4% in ‘S1’ and 2.8% in ‘Naxos’, highlighting genotype dependence. In parallel, a transient expression system was established using cotyledon-derived protoplasts and electroporation-mediated DNA delivery. GFP expression was confirmed through fluorescence microscopy, confocal imaging, and Western blotting. These protocols provide a robust toolkit for broccoli genetic manipulation, facilitating molecular biology studies in the native plant, functional genomics and genome-editing strategies, including CRISPR-based approaches. Full article

Lab-on-a-Chip (LoC) and microfluidic technologies are rapidly reshaping the development pipeline for nano drug delivery systems (DDSs) by enabling precise control of physicochemical properties, high-throughput screening, and integrated biological evaluation within miniaturized platforms. This review synthesizes recent advances in microfluidic principles, fabrication strategies, and sensing modalities that facilitate continuous flow synthesis, real-time characterization, and adaptive formulation of nanoparticles. We highlight how LoC-enabled systems improve monodispersity, reproducibility, and tunability of liposomes, polymeric nanoparticles, and metallic nanocarriers, while providing powerful tools for assessing pharmacokinetics, drug release, and systemic responses using organ-on-chip (OoC) models. Emerging trends, including AI-driven autonomous optimization, stimuli-responsive materials, 3D-printed hybrid architectures, and self-powered portable devices, are discussed in the context of future integrated nano-pharmaceutics platforms. Despite existing challenges related to biocompatibility, standardization, data integration, and translation to industrial and clinical applications, the synergistic evolution of LoC engineering and nanomedicine holds transformative potential for personalized and next-generation therapeutic strategies. Full article

Background: Smart urban logistics has emerged as a key element of sustainable city development, with direct effects on economic performance, environmental quality, and urban livability. Issues with traffic, pollutants, infrastructure strain, and last-mile delivery efficiency have become more pressing due to rapid urbanization and the expansion of e-commerce. In this regard, underground or enclosed corridor-based tube-based freight transit systems have surfaced as a viable smart infrastructure option for automated and low-impact commodities delivery. Methods: This study adopts an analytical literature review complemented by a structured case study analysis to examine the potential role of tube-based freight transport systems in future urban logistics. Key technological concepts, including pneumatic tubes, automated capsule transport, and integration with digital platforms, the Physical Internet, and smart city management systems, are examined through a structured analytical review of the literature. Results: The outcome of the reviewed studies indicates that tube-based systems can contribute to congestion alleviation, emission reduction, and improved delivery reliability by shifting selected freight flows away from surface transport networks. However, governance frameworks, infrastructure integration, and institutional coordination mechanisms continue to have a significant impact on claimed performance outcomes. Conclusions: Tube-based freight systems represent a promising but conditional pathway toward smarter and more sustainable urban logistics. Their large-scale deployment is forced by high capital costs, standardization challenges, regulatory uncertainty, and social acceptance issues. Coordinated investment plans, encouraging legal frameworks, and integrated urban planning techniques in line with smart city goals are needed to overcome these obstacles. Full article

Low-concentration methane emissions from landfills, manure management, wastewater treatment, and ventilation streams are difficult to mitigate using conventional capture and oxidation because of high air-to-fuel ratios, variable flows, and unfavorable economics. Methanotrophic bioreactors provide an aerobic biological route to oxidize methane at ambient conditions and, in selected cases, enable valorization into biomass and bioproducts. This review synthesizes methanotrophic reactor technologies for dilute methane, emphasizing the design and operational constraints that control performance. We classify systems into (i) fixed-film gas–solid configurations (biofilters, biocovers, biotrickling filters, and bioscrubbers), (ii) suspended-growth gas–liquid reactors (stirred tanks, bubble columns, and loop/airlift designs), (iii) membrane-based and intensified contactors that decouple methane and oxygen delivery and enhance mass transfer, and (iv) hybrid and in situ approaches for diffuse sources. This review presents key metrics and discusses how mass transfer, moisture and temperature control, nutrient supply, and microbial ecology interact to define achievable removal. We further summarize recent techno-economic and life-cycle studies to identify dominant cost drivers, particularly air handling and gas–liquid transfer, and the concentration regimes where biological oxidation is competitive with catalytic or thermal alternatives. Full article

The purpose of this study is to develop and validate a System Dynamics (SD) model that illustrates how Artificial Intelligence (AI), including generative AI, alters project lifecycle behavior under a hybrid agile–predictive governance approach. The study method uses SD model to operationalize the PMBOK performance domains as an interconnected system of stocks, flows, and feedback loops. These constructs and their interaction represent delivery progress, stakeholder engagement, team capacity, measurement accuracy, governance alignment, and uncertainty exposure. Planning effectiveness is treated as an emergent performance indicator arising from the interaction of the planning-related feedback structures. The proposed model embeds AI levers for planning, risk, measurement, stakeholder sensing, and team support. A calibrated baseline model representing conventional project dynamics was validated in two ways. First it was validated structurally against PMBOK guidance and the SD literature. Secondly, it was validated behaviorally against stylized project trajectories. The AI-augmented variant was then simulated under identical initial conditions to assess marginal effects. Across multiple scenarios, AI integration reduced peak uncertainty exposure by up to 33%. Also, the AI-augmented system showed reduced planning effort by 15%, and improved monitoring and risk sensing by accelerating feedback and reducing delays by 25%. AI also improved measurement accuracy trajectories and accelerated cumulative delivery while lowering volatility in work completion rates. Governance coherence and development approach alignment improved, while stakeholder engagement and team capacity showed smaller changes. The results demonstrate that AI primarily acts as an enabler that strengthens high-impact feedback loops in planning, monitoring, and risk sensing within a hybrid methodology. AI also delineates boundaries where managerial judgment and cultural change remain critical for effective framework validation. Full article

Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may disrupt oncologic treatment delivery. The oral cavity imposes stringent constraints on regenerative biomaterials—continuous salivary flow, high microbial load, and repeated mechanical shear—such that clinical success depends on reliable mucoadhesion/wet adhesion, barrier function, mechanical compliance, and safe, spatially confined bioactivity. This PRISMA-informed evidence-mapped structured narrative review provides an evidence map and structured qualitative synthesis of hydrogel and scaffold platforms relevant to post-OSCC care, spanning clinically used mucoadhesive barrier formulations through emerging wet-adhesive multifunctional patches, acellular matrices, and tissue-engineered oral mucosa (TEOM) constructs. Clinically, the strongest evidence base remains barrier-forming gels and liquids that reduce OM pain and improve oral function during active therapy, establishing performance benchmarks for intraoral retention and patient-reported benefit. Preclinical studies are rapidly expanding toward multifunctional designs that integrate antimicrobial, anti-inflammatory, pro-epithelialization, and pro-angiogenic cues. However, a pervasive limitation is the inconsistent use of OSCC-relevant models (e.g., irradiated/xerostomic tissue beds), standardized functional endpoints (e.g., oral intake, durability under mastication, and neurosensory outcomes), and explicit oncologic safety evaluation, which severely compromises translational validity. For reconstructive applications, dermal matrices and early TEOM reports suggest feasibility for selected defects, but controlled comparative trials and scalable manufacturing pathways remain limited. Translational priorities include oncologic-by-design bioactivity (time-limited, locally confined cues), clinically anchored outcome reporting, and quality-by-design manufacturing aligned with device/combination/advanced-therapy regulatory requirements. Full article

Magnetic nanoparticles represent the next-generation drug delivery systems, enabling drug targeting to specific organs without adverse effects on the body and with a controlled release rate. Their strengths are represented by biocompatibility, low cost, and easy drug loading; some drawbacks are aggregation and poor stability in biological media. In the present work, we synthesized magnetic core–shell structures with a magnetite core coated with layered double hydroxides (LDHs) based on Mg²⁺ or Zn²⁺ and Al³⁺ ions and loaded with meloxicam, a poorly water-soluble anti-inflammatory drug. Several syntheses have been attempted to obtain iron oxides based on the only magnetite phase. The combined use of different characterization techniques allowed us to reveal that the best product, showing the crucial room temperature superparamagnetism and a good level of compositional uniformity, was obtained from co-precipitation in nitrogen flow. The next LDH coating was successful, even if the hybrids showed the occurrence of aggregation. The drug was mainly adsorbed onto the LDH surfaces, as shown by the X-ray diffraction and Infrared Spectroscopy techniques. The loaded meloxicam amount was low, but the subsequent release into simulated body fluid could be prolonged for 4 days. Our study provides a proof of concept about the importance of a thorough characterization of the nanocomposite hybrids and their possible use for tricky drugs, such as those of class II of the Biopharmaceutical Classification System. Full article