Search Results (1,759)

Offshore high-temperature steam flooding suffers severe steam channeling, uneven steam intake and low thermal efficiency, while conventional profile control agents fail to adapt to coupled harsh environments of 200–350 °C high temperature, ultra-high salinity and continuous steam shear. Existing reviews mainly focus on onshore thermal reservoirs or single foam/gel materials, lacking a targeted, gel-oriented systematic review matching unique offshore platform constraints. Guided by the integrated framework of “flow control–diversion–enhanced sweep efficiency”, this work establishes a six-dimensional quantitative screening standard and unified performance comparison database to systematically review foam, gel, particle, thermo-responsive and composite profile control systems. Differing from petroleum engineering-oriented summaries, this paper subdivides high-temperature gels into six categories from a polymer material perspective, elaborating their crosslinking mechanisms, thermal rheology and cyclic steam degradation rules; the inherent advantages, limitations and offshore applicable boundaries of each medium are quantitatively compared, with special emphasis on the unique “deep migration followed by in situ thermal activation” mechanism of thermo-responsive materials. Composite systems relieve single-material defects via multi-mechanism synergy yet face complicated on-site deployment barriers. Three core bottlenecks restricting field application are identified: the irreconcilable trade-off between deep propagation and stable plugging, large deviation between static aging results and dynamic anti-scouring performance, and exclusive engineering limitations of offshore platforms. A dedicated standardized dynamic laboratory evaluation scheme for cyclic steam flooding is proposed to narrow lab-field performance gaps. Future research priorities include salt-resistant thermally responsive composite gel modification, low-cost multi-component compound formula optimization, unified dynamic evaluation criteria and staged material matching guidelines to realize balanced performance of high-temperature tolerance, deep delivery and offshore operability. Full article

Transcranial magnetic stimulation-electroencephalography (TMS–EEG) biomarkers have recently become available as a means to obtain new understanding of the causal chains of neuronal signaling in the brain. This is a key piece in the puzzle of how the brain is organized and how it works. Using dMRI tractography, we can map the circuit beneath a chosen cortical target; TMS can then stimulate it, and EEG records responses that reflect—and may even be caused by—activity in that structural circuit. The chain of events after stimulus delivery can be observed and quantified using current neuroimaging and TMS–EEG technology, a matter of tremendous relevance on how to approach novel therapeutic approaches in clinical conditions. Herein, we elaborate upon a perspective of how groundbreaking multi-locus TMS (mTMS) technology associated with EEG and multimodal neuroimaging can be applied to modulate the flow dynamics of the glymphatic system (GS). The enhancement of the GS waste clearance functionality has been shown to improve significantly symptom severity in neurodegenerative disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD) or long COVID. In this perspective paper, we consider that next-generation therapeutics using versatile technologies such as noninvasive neuromodulation and neuroimaging will provide important benefits in public health and in how society can address the management of these difficult-to-deal-with ailments more effectively. Full article

Background: Oncolytic viruses (OVs), a promising anti-cancer therapeutic, replicate more efficiently in cancer cells rather than in healthy cells due to the alterations in antiviral response mechanisms and dysregulation of signaling pathways. Vesicular stomatitis virus (VSV) is known for low pathogenicity, tropism to various cancer cells, and the ability to lyse cells in the hypoxic tumor microenvironment (TME). Targeted delivery of immune checkpoint and co-stimulatory molecules can enhance the anti-tumor immune response and remodel the immunosuppressive TME. The aim of this study was to compare the activity of rVSV-GFP with rVSV, encoding the programmed cell death protein 1 (PD-1) and tumor necrosis factor ligand superfamily member 9 (4-1BBL). Methods: The oncolytic efficacy of these rVSV variants used at 10⁵, 10⁶, and 10⁷ TCID50 was evaluated at 24 and 48 h post-infection by flow cytometry in a panel of mouse and human cancer cell lines. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of certain genes at 12 and 48 h post-infection. Results: Murine hepatocellular carcinoma (H22) and human melanoma (A375) or human lung carcinoma (A549) were the most sensitive to rVSV therapy cell lines. The higher relative expression of the antiviral response genes RIG-I and IFIT1 within each biological species (mouse or human) correlated with lower sensitivity to rVSV. No such effect was observed for the type I interferons (IFNs), despite their proposed key role in resistance to OV therapy. Conclusions: H22, A375, and A549 are more susceptible to the oncolytic activity of the novel rVSV-PD-1-4-1BBL. Full article

Background/Objectives: Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional small molecules that induce ubiquitin–proteasome–mediated degradation of target proteins and have matured from proof-of-concept chemistry to a clinically validated therapeutic modality, with the first Phase 3 readout reported in 2025. A systematic bibliometric analysis covering this pivotal-trial era, however, has been lacking. This study aimed to map the historical trajectory, current research front, and emerging frontiers of PROTAC research. Methods: We analyzed 2630 PROTAC-related publications indexed in the Web of Science Core Collection (WoSCC) from 2001 to 2025 using a combined toolkit of CiteSpace, HistCite, the Alluvial Generator, and R (ggplot2), covering co-occurrence networks, burst detection, keyword clustering, citation historiography, alluvial flow analysis, and reference co-citation timeline visualization. Results: China and the USA led global output, and the Chinese Academy of Sciences, China Pharmaceutical University, and Harvard University were the most productive institutions; the Journal of Medicinal Chemistry was the leading publishing venue, and Alessio Ciulli, Jian Jin, and Craig M. Crews anchored the author network. Keyword burst analysis showed that early research centred on E3 ubiquitin ligase recruitment and small-molecule PROTAC design, whereas the current hotspots, resolved through keyword clustering and co-citation timelines, included structural basis and ternary complex design, EGFR-directed degradation, oral bioavailability optimization, applications in multiple myeloma and Alzheimer’s disease, tumour-targeted delivery, and computational/AI-driven design. Conclusions: This study extends the bibliometric record of PROTACs across 2001–2025 and identifies oral bioavailability, E3 ligase repertoire expansion, and CNS-penetrant degrader design as the emerging frontiers likely to shape the next phase of the field. Full article

Moyamoya disease is a progressive steno-occlusive cerebrovascular disorder in which cerebral perfusion may become highly dependent on systemic arterial pressure, arterial carbon dioxide tension, and collateral flow. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization procedure that promotes neovascularization over weeks to months but does not immediately augment cerebral blood flow intraoperatively. Anesthetic management therefore requires preservation of cerebral oxygen delivery during a period of persistent physiologic vulnerability. This narrative review presents a practical perioperative framework for EDAS anesthesia, emphasizing maintenance of mean arterial pressure near baseline or modestly above baseline, avoidance of hypotension and hypovolemia, normoxia, normothermia, and careful regulation of carbon dioxide. Hyperventilation should be avoided because hypocapnia can reduce cerebral blood flow through vasoconstriction, while excessive hypercapnia may contribute to regional maldistribution or steal physiology. Raw electroencephalography may provide cortical ischemia surveillance where available, whereas somatosensory evoked potentials, motor evoked potentials, near-infrared spectroscopy, and transcranial Doppler should be considered adjunctive and institution-dependent. A structured algorithm that integrates hemodynamics, ventilation, oxygen delivery, anesthetic depth, neuromonitoring, and surgical communication may support the timely recognition and correction of intraoperative hypoperfusion. Full article

Background/Objectives: Glioblastoma multiforme (GBM) treatment is limited by tumor hypoxia and poor specificity of therapeutic agents. To address these challenges, we developed brain-targeted liposomes co-encapsulating 5-aminolevulinic acid (5-ALA) and catalase (CAT), termed brain-targeted 5-ALA-CAT liposomes (BACL), which were surface-modified with the Angiopep-2 ligand to enhance blood–brain barrier penetration and achieve multimodal therapy combining targeted delivery and oxygen generation. Methods: BACL was prepared and characterized. Tumor targeting was verified by flow cytometry and in vivo imaging. In vitro antitumor activity was evaluated by wound-healing assay, colony formation assay, live/dead staining, MTT assay, and Western blotting. In vivo efficacy, apoptosis, and safety were assessed in a subcutaneous xenograft model. Transcriptome sequencing and qRT-PCR were employed to identify molecular mechanisms and novel targets. Results: BACL exhibited favorable physicochemical properties (size: 122.4 nm, PDI: 0.189, zeta potential: −12.3 mV) and spherical morphology as observed by TEM, with encapsulation efficiencies of 51.2% for 5-ALA and 43.8% for CAT. Compared with unmodified 5-ALA, BACL increased the cellular uptake efficiency by 1.6-fold in glioma cells while maintaining catalytic stability for sustained oxygen generation. In vitro experiments demonstrated that BACL significantly inhibited glioma cell migration, colony formation, and cell viability, and induced apoptosis. In a subcutaneous xenograft tumor model, BACL-mediated photodynamic therapy (PDT) achieved a tumor growth inhibition rate of 52%, with apoptosis induction via regulation of Bcl-2, Bax, and p53 expression, and no obvious toxicity to major organs was observed. Transcriptomic analysis combined with qRT-PCR validation revealed that BACL activates multiple antitumor signaling pathways, including targeted inhibition of IL-10 and CXCL13 to disrupt cytokine–receptor interactions, as well as coordinated regulation of S100A3 and IGSF-9 expression to suppress glioma progression. Conclusions: These multimodal actions enhanced PDT efficacy while remodeling the tumor microenvironment. Our findings position BACL as a promising therapeutic platform integrating targeted delivery, hypoxia alleviation, and immunomodulation for GBM therapy. Full article

Bacterial infections pose a serious threat to human health, and antibiotics remain the first-line therapeutic agents in clinical practice. However, the vast majority of antibiotics lack the ability to penetrate cell membranes, which severely limits the number of clinically available options for treating intracellular bacterial infections. Developing efficient intracellular antibiotic delivery strategies is therefore of considerable clinical significance, both for reducing antibiotic dosage and for expanding the repertoire of drugs applicable to intracellular infections. To address this challenge, we constructed a protein-based delivery platform mediated by a cell-penetrating miniprotein for efficient intracellular antibiotic delivery. In this system, bovine serum albumin (BSA), which possesses broad antibiotic-binding capability, was employed as the drug carrier, while the cell-penetrating miniprotein ZF5.3, which is capable of endosomal escape, served as the transmembrane delivery mediator. ZF5.3 was conjugated to BSA via a bioorthogonal reaction, and ceftriaxone (CRO) was selected as the model antibiotic to construct a nanoscale delivery system. The binding interaction between CRO and BSA was characterized using UV-Vis, HPLC, and molecular docking techniques. The assembly of the ZF5.3–BSA delivery platform was confirmed by UV-Vis absorption spectroscopy and gel electrophoresis. Intracellular delivery efficiency was evaluated by confocal fluorescence imaging and flow cytometry, and the results demonstrated that ZF5.3 conjugation enhanced intracellular protein delivery efficiency by over 5-fold. Fluorescence co-localization analysis revealed that ZF5.3-mediated cargo is mainly distributed in the cytoplasm and does not completely co-localize with lysosomal markers, suggesting its ability to effectively escape from lysosomes. An intracellular infection model using Staphylococcus aureus was established. Colony-forming unit (CFU) counting experiments confirmed that the delivery system significantly enhanced the intracellular antibacterial activity of ceftriaxone. CCK8 cytotoxicity assays confirmed that the system is non-toxic to cells. Full article

Background/Objectives: The aim of current study was the significant improvement of both the flowability and the compressibility of mesoporous silica microparticles (MSMs), to enable the formulation a potential drug delivery system. MSMs are of emerging interest in the pharmaceutical industry, due to their numerous advantages and versatile applicability, such as improvement in aqueous solubility and epithelial permeability, thus enhancing the oral bioavailability of drugs. However, the formulation of these types of materials has been a major challenge. This problem originates from poor powder flow characteristics due to particle properties. Methods: A binder-free high-shear wet granulation (HSWG) process was performed to improve the flowability and compressibility of the model material, meanwhile preserving its porosity. The prepared granules were characterized by particle size, size distribution, yield percentage, particle morphology, porosity, powder flowability, crushing strength, and stability. Micro-CT measurements were performed to examine the structure of the granules and to see the internal segmentation resulted by the two-step granulation process. The granules were compressed into tablets to evaluate the compressibility behavior based on the models of Kawakita and Walker. The physical parameters of the compressed tablets, such as breaking hardness, tensile strength, and thickness, were tested. Results: The prepared granules were evaluated successfully according to the mentioned properties and found to be satisfactory compared to the raw materials. The binder-free method appeared to be effective, thus the use of binders may be avoided if the process is designed well and critical process parameters (CPPs) selected carefully. The granules showed good stability over a one-year testing period. The micro-CT test also verified the success of the initial concept of preparing core–shell structured granules, and enabled the determination of macropores. Nevertheless, the results were completed with BET measurements to determine specific surface area of the granules. Conclusions: The effect of the critical process parameters of the granulation process on all the mentioned attributes was investigated and since major differences were observed between the batches, the effect of the selected CPPs were also verified. Full article

This research analyzes the wavy, axisymmetric flow of a Ree–Eyring non-Newtonian nanofluid, infused with motile microorganisms, within a porous, tapered cylindrical channel under a transverse magnetic field. This investigation presents a theoretical framework that may inform the improvement of energy efficiency and thermal management in biomedical engineering applications, such as drug delivery systems and microfluidic biosensors. The work provides an extended insight by a contribution to the evaluation of entropy generation, explicitly considering the influence of motile microorganisms, thereby bridging a gap in the existing literature. The comprehensive physical model further incorporates the combined effects of Joule heating, viscous dissipation, nonlinear thermal radiation, and chemical reactions. Methodologically, the governing nonlinear equations of the system were rendered tractable under long-wavelength and low-Reynolds-number assumptions and subsequently solved using the numerical Runge–Kutta–Fehlberg technique. The key conclusion is that, based on the present numerical model, careful selection of magnetic field strength and microorganism motility parameters may reduce irreversible energy losses, potentially improving the net usable work in advanced nanofluid transport systems for biomedical applications, subject to experimental validation. The most significant finding reveals that the magnetic field serves as a dual-purpose control parameter: increasing its strength boosts total entropy generation by 20–30% while simultaneously raising the Bejan number, confirming heat transfer as the dominant irreversibility mechanism in the system. Additionally, nanoparticle concentration diminishes substantially with elevated chemical reaction rates and Schmidt numbers, while microorganism density is highly sensitive to the Péclet number, which causes flow disruptions. Full article

Nanoemulsion (NEM) is an effective adjuvant and delivery system for vaccines and nucleic acids, capable of inducing immune responses against diverse pathogens. Background/Objectives: Conventional NEM manufacture uses multi-step operations, typically high-shear homogenization and then microfluidization (HSHM), thereby increasing process complexity and contamination risk. As water-rich colloidal dispersions, NEM is prone to microbial proliferation and droplet coalescence; freezing further disrupts microstructure, causing phase fusion and separation, so NEM adjuvants are often stored separately from antigens in multi-vial formats. Lyophilization could reduce cold-chain dependence and enable single-vial products, but there is no systematic study on lyoprotectants comparation and process optimization of lyophilized NEM. Methods: An impingement jet mixing (IJM) process was evaluated as a simplified, scalable route for NEM production. Key IJM parameters, including flow ratio, total flow rate, preparation temperature, microchannel type, and shear mode—were examined to match attributes of conventional HSHM. Lyophilized and reconstituted NEM were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and/or in vitro potency to inform lyoprotectant selection, and Taguchi Design of Experiment (DOE) methodology guided lyophilization processes. Results: IJM yielded NEM with droplet size, polydispersity index (PDI) and morphology comparable to HSHM, with higher throughput and fewer unit operations. Optimized lyophilization technique with designed lyoprotectant and process formed closed structures to prevent the easy-to-flow monolayer of the emulsion from fusing, producing robust and stable NEM. Conclusions: Coupling IJM with targeted lyophilization establishes a scalable, lower-risk manufacturing paradigm for NEM that preserves critical quality attributes, reduces cold-chain reliance and enables single-vial adjuvanted vaccine formats with tangible industrial and clinical benefits. Full article

This paper presents the field deployment and performance evaluation of a New Radio Vehicle-to-Everything (NR-V2X) Cooperative Intelligent Transportation System (C-ITS) test corridor over a 5G stand-alone (SA) private network, implemented on a 40 km highway in Istanbul, Turkey. The deployment integrates 19 dual-sector gNBs, commercial off-the-shelf (COTS) core network components, and an O-RAN-compatible Rel. 17 architecture and evaluates six ETSI-compliant C-ITS scenarios under a systematic 3 × 3 experimental matrix spanning three vehicle speeds and three traffic density categories. Key quantitative findings include the following: (i) 98.9% of the corridor achieves the target RSRP of −110 dBm, confirming coverage viability; (ii) five of the six scenarios satisfy ETSI end-to-end latency requirements across all tested conditions, with the packet delivery ratio remaining above 94% throughout; and (iii) the Emergency Vehicle Approaching (EVA) scenario meets its stringent 20 ms latency requirement exclusively under free-flow conditions (μ = 14.7 ms) and progressively exceeds it under medium- and high-density traffic (μ = 26.6 ms and μ = 40.1 ms, respectively). These results provide quantitative evidence that MEC integration is a necessary architectural complement to the 5G SA private network for ultra-low-latency safety services and establish a reproducible reference architecture for public highway C-ITS deployments. Full article

We conducted a theoretical analysis on the diffusiophoretic motion of a dielectric droplet in a cylindrical pore in the presence of an induced diffusion potential, such as that in a NaCl electrolyte solution. The fundamental electrokinetic governing equations are solved using a patched pseudo-spectral method based on Chebyshev polynomials, coupled with a geometric mapping scheme to handle the irregular solution domain. The impact of the boundary confinement effect on droplet mobility is examined in detail. Interesting electrokinetic phenomena are found in this work, such as mobility reversal in narrow cylindrical pores with the droplet moving against the direction expected based on the classical Coulomb electrostatic law due to the strong boundary confinement effect. Moreover, “solidification phenomenon” is also found at some specific pore radius where the droplets move as rigid particles with no interior recirculating vortex flows regardless of the droplet viscosities. Corresponding critical points of ${\mathrm{R}}_{\mathrm{w}}^{\mathrm{*}}$, the ratio of droplet radius to the cylindrical radius are found where the spinning orientation on the droplet surface changes each time as it passes them. The profound boundary confinement effect, both electrostatically and hydrodynamically, is responsible for these peculiar phenomena. The results presented here have direct applications in microfluidic and nanofluidic operations as well as drug delivery applications. Full article

Background: Uncontrolled hemorrhage, especially at non-compressible sites, remains a major cause of preventable trauma deaths. This study reports the development of fibrinogen-loaded calcium carbonate (CaCO₃) microparticles that combine hemostatic activity with self-propelling capability for targeted delivery against blood flow, with a focus on understanding formulation-dependent trade-offs among particle yield, protein loading, clotting performance, and transport behavior. Methods: Microparticles were synthesized via a precipitation method using different carbonate sources and characterized for yield, morphology, size, and fibrinogen encapsulation. Hemostatic function was assessed using rotational thromboelastometry (ROTEM) in fibrinogen-deficient plasma. Propulsion behavior was evaluated following exposure to protonated tranexamic acid (TXA⁺), which triggers CO₂ generation. Particle size and encapsulation were examined by microscopy and fluorescence imaging. Results: The precipitation method produced spherical micrometer-sized particles, with fibrinogen inclusion reducing yield and particle size relative to unload controls. Fluorescence microscopy confirmed successful encapsulation. Encapsulation efficiency varied with formulation, with sodium carbonate-based particles showing higher relative fibrinogen loading. ROTEM analysis demonstrated that fibrinogen-loaded particles significantly improved clot formation, increasing maximum clot firmness compared to fibrinogen-free particles, although performance remained formulation-dependent. TXA⁺-triggered propulsion achieved maximum speeds up to 4.221 cm/s. Fibrinogen-loaded particles exhibited longer activation lag times than unloaded particles, indicating a trade-off between hemostatic functionality and propulsion kinetics. Conclusions: Fibrinogen-loaded CaCO₃ microparticles exhibit both hemostatic activity and chemically triggered motion in vitro. The study identifies key formulation-dependent trade-offs between particle yield, fibrinogen loading, clotting performance, and propulsion behavior. While these findings support the feasibility of combining localization and clot stabilization mechanisms, further studies under physiologically relevant flow conditions and in vivo models are required to evaluate their potential for active delivery in non-compressible hemorrhage. Full article

Successful project delivery largely depends on effective progress management to ensure schedule reliability and resource efficiency. Conventional manual and paper-based approaches remain inefficient and error-prone, often causing fragmented data and poor collaboration among stakeholders. To overcome these limitations, this study proposes a computer vision–blockchain integrated framework for closed-loop construction progress management within the Plan–Do–Check–Act (PDCA) cycle. This system supports an automated, end-to-end workflow in which UAV-captured images are processed by a computer vision model, digitally signed, and verified on a blockchain ledger, triggering smart contract-based schedule deviation alerts to relevant stakeholders. An enhanced digital signature scheme ensures data integrity during off-chain and on-chain transitions, while self-executing smart contracts coordinate schedule submissions, progress reporting, and deviation detection. Implemented on Hyperledger Fabric and validated through a case study, the framework demonstrates transparent data flow and strong performance in detection accuracy, latency, and throughput. By shifting progress management from passive reporting toward proactive control, this study provides a replicable, transparent, and tamper-resistant solution for multi-stakeholder construction progress governance. Full article

Background: Conventional drug delivery systems often lead to fluctuating plasma concentrations (“Peak and Trough” phenomenon), causing toxicity or inefficacy. Microfluidics has emerged as a revolutionary tool to overcome, among other applications, the limitations of conventional bulk encapsulation methods, such as polydispersity and poor reproducibility. Methods: A systematic review of the literature published between 2020 and 2025 was conducted to evaluate the application of microfluidics in the synthesis of advanced nanomedicines. The review focused on Lipid Nanoparticles (LNPs), Polymeric Nanoparticles (PNPs), and Hydrogel Microspheres. Results: Microfluidics enables the production of monodisperse particles with precise control over geometry and drug loading stoichiometry. Key therapeutic applications include oncology (passive and active targeting), gene therapy (mRNA vaccines), and regenerative medicine (diabetic wound healing). Conclusions: While microfluidics offers superior quality control compared to bulk methods, industrial scalability remains the primary challenge, currently addressed through parallelization and continuous flow strategies. Full article