TICAM1 inhibits angiogenesis and accelerates inflammation in the healing of diabetic wounds via the NF-κB pathway.

Development and characterization of lipid based solid dispersion of quassinoid enriched fraction of Simarouba glauca for enhanced lipid membrane permeability in MCF7 breast cancer cells

Development of zein/ethyl cellulose composite films for sausage smoking: Effects on smoke-derived volatile compounds.

ABSTRACT This article examines how subregional cooperation initiatives in Southeast Asia, celebrated for promoting ‘borderless’ economic integration, re‑scale and re‑narrate long‑standing projects of enclosure that deepen the marginalisation of maritime communities. Focusing on the Singapore–Johor–Riau (SIJORI) Growth Triangle and the Brunei–Indonesia–Malaysia–Philippines East ASEAN Growth Area (BIMP‑EAGA), it traces how regional growth zones build on colonial and national histories of surveillance, sedentarisation, and dispossession while reorganising them through cross‑border institutions and development rhetoric. Drawing on the concept of selective border permeability – where borders open to state elites and investors but tighten around communities such as the Orang Laut and Bajau Laut – the analysis shows how these initiatives extend uneven geographies of mobility into the sea. By bringing critical geopolitics into conversation with the original concept of blue agrarianisation, the article argues that subregional cooperation reimagines the sea as both a ‘borderless’ investment frontier and a landscape of intensified regulation. Juxtaposing SIJORI and BIMP‑EAGA, the study demonstrates how regional projects selectively open borders for capital while consolidating state authority, reproducing older forms of enclosure in new, regionally articulated ways.

Small-molecule degraders eliminate disease-driving proteins by hijacking the ubiquitin-proteasome system. To achieve cellular activity, protein degraders must perform a series of consecutive steps involving cell permeability, binary target engagement, and formation of a ternary complex with the target protein and a ubiquitin E3 ligase, followed by protein ubiquitination, culminating with protein degradation. Monitoring each mechanistic step of a degraders' mode of action is important to confirm its bona fide cellular activity and guide rational design and optimization. In this review, we offer an overview of how degraders work and outline the key parameters and associated methods to study each step of the mechanism. We compare and contrast biophysical and cellular in vitro assays and provide a concise framework for prioritizing and mapping them to decision stages. We also discuss the main factors affecting degrader's cellular performance and principles that have emerged to guide drug design.

Green and sustainable dual-pathway strategies for high-efficiency photoconversion of ergosterol to vitamin D₂ from agaricus bisporus.

Shear-cytokine crosstalk is a determinant of SARS-CoV-2 induced endothelial pathophysiology and thrombosis in human vessel-chips.

Age-related disorders known as neurodegenerative illnesses are defined by uncontrolled neuronal loss that gradually impairs brain function. The majority of age-related neurodegenerative disorders are caused by dementias, in particular. Nowadays, the neurodegenerative disorders are not limited to age and are reported in all age groups. The drug delivery to treat the neurodegenerative disorders is challenging due to the presence of the blood-brain barrier (BBB). A critical literature review has been conducted across databases such as Scopus, Embase, Cochrane, and PubMed. Blood-brain barrier, neurodegenerative disorders, novel drug delivery system, and targeted drug therapy were the search terms. Neurodegenerative Diseases (NDD) impact the peripheral nervous system, nerve cells, muscles, and the nerve-muscle junction. This term broadly encompasses cognitive disorders, such as Alzheimer's disease, Lewy body dementia, frontotemporal dementia, and vascular dementia. Additionally, other neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and spinocerebellar ataxias predominantly impair motor system function and nerves in the limbs. The existing therapeutic approaches to treat neurological diseases exhibit limited efficacy due to the BBB. This highly selective semipermeable membrane permits vital nutrients to enter the brain while blocking the potentially harmful toxins. It makes it very challenging to get medications into the brain. There are several effective approaches to deliver drugs to the brain (nanocarrier systems, intranasal administration, and focused ultrasound) to address the limitations of conventional treatments. This review discusses neurodegenerative disorders, brain anatomy/physiology, barriers to drug delivery, and strategies to overcome these limitations.

The Blood-Brain Barrier (BBB) poses a formidable challenge for drug delivery to the Central Nervous System (CNS) due to its selective permeability and robust defense mechanisms. This review provides a comprehensive examination of the anatomical structure, physiology, and physiological challenges of the BBB, along with innovative approaches for overcoming these barriers to enhance CNS drug delivery. The BBB is primarily composed of endothelial cells, pericytes, and astrocytic end-feet, reinforced by tight junctions that tightly regulate the passage of substances into the brain parenchyma. Various transport mechanisms, including carrier-mediated transport, receptor-mediated transport (e.g., via LDL and transferrin receptors), absorptive-mediated transport, and active efflux transport, govern the selective influx and efflux of molecules across the BBB to maintain CNS homeostasis. Biological approaches harness endogenous transport mechanisms to facilitate drug delivery across the BBB, while chemical approaches leverage nanotechnology to engineer nanoparticles capable of traversing the barrier. These include liposomes, solid-lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, each designed with specific parameters such as particle size, shape, and surface charge to optimize drug delivery. Drug loading strategies, such as covalent bonding and non-covalent adsorption, enhance the encapsulation and release of therapeutic agents from nanoparticles. Furthermore, the incorporation of ligands facilitates receptor targeting and protein corona formation, enhancing nanoparticle properties and improving BBB penetration. By synthesizing recent advancements in BBB permeation strategies, this review aims to provide insights into the development of effective therapies for neurological disorders, ultimately advancing the field of CNS drug delivery.

Pseudomonas aeruginosa is a major global health concern due to its multidrug resistance (MDR), necessitating the urgent development of novel therapeutic strategies. Understanding the molecular basis of resistance in clinical isolates is critical for designing next-generation antimicrobials. This study analysed recent clinical isolates of P. aeruginosa obtained from the NCBI for their resistance gene and virulence factor profiles. Among the virulence-associated targets, MvfR, a key transcriptional regulator of quorum sensing and biofilm formation, was prioritized based on its functional relevance. AI modelling of MvfR identified from the genome analysis was performed, followed by molecular docking against library of compounds, phylogenetic comparisons to compare with previously identified homologs, ADMET-profiling, 500 ns molecular dynamics (MD) simulations, binding free energy, and Density Functional Theory (DFT). Genes critical for antimicrobial resistance, drug targeting, and virulence factors were identified across multiple databases. The antimicrobial resistance genes and receptors revealed key resistance mechanisms, including antibiotic-inactivating enzymes, efflux pumps, quorum sensing, and alterations in cell wall charge or permeability. Notably, (S)-1-(2-(difluoromethyl)-1H-benzo[d]imidazol-5-yl)-3-(2-hydroxy-2-(pyridin-4-yl)ethyl)urea exhibited the highest docking score against MvfR. DFT and MD simulations over 500 ns demonstrated stability of the top ligands, supported by favourable molecular stability parameters such as RMSD, SASA, RMSF, and Rg plots. Furthermore, the top-ranking ligands satisfied Lipinski's rule of five, suggesting favourable drug-like properties. This study provides an integrated computational characterization of MvfR in recent P. aeruginosa isolates and identifies genetic variations that may influence disease manifestation. It further demonstrates an integrative computational strategy to accelerate discovery of promising antimicrobial agents against multidrug-resistant bacteria.

ABSTRACT The integration of carbon dioxide (CO 2 ) with green hydrogen (H 2 ) for methanol synthesis presents a viable alternative to conventional fossil fuel‐based production routes under the background of carbon emission reduction. However, the synthesis reaction is thermodynamically limited and the byproduct of H 2 O would deactivate catalysts. The water removal membrane is introduced to improve the synthesis process and a coupled multiphase catalytic membrane reaction model has been established to investigate the enhancement of methanol synthesis due to the water removal in CO 2 hydrogenation. Results demonstrate that the selective permeability of water removal membrane both for countercurrent and co‐current flow lead to the significant improvement to the CO 2 conversion and methanol yield. The former flow type exhibits higher ΔP H2O around the outlet of the reaction channel (RC), higher maximum for H 2 O concentration in the sweep gas channel (SC), but may cause reverse H 2 O permeability around the inlet of RC, while the later flow shows a slightly lower average driving force but a relatively smooth water removal process. The optimization analysis show that the performance of membrane reactor can be significantly improved with the increase of reaction temperature and, pressure or H 2 /CO 2 . For the membrane reactor with co‐current flow at 513 K, 5.5 MPa and 0.015 m/s, CO 2 conversion increase up to 50% and methanol yield up to 56%, which are much higher than that of fixed‐bed reactor.

Biomanufacturing is being explored as a potential solution for improved space logistics in austere environments. One potentially useful tool is electroporation-the delivery of exogenous DNA into cells using pulsed electric fields to increase cell membrane permeability. Electroporation has the potential to enable tunable bioreactors in a space environment through the targeted delivery of nucleic acids encoding proteins of interest and may also present a solution for disinfection, purification, and biomolecule extraction without requiring disposable reagents. Unfortunately, electroporation has not been studied using cells adapted to microgravity conditions, and it is possible that well-known cellular adaptations to microgravity will alter electroporation outcomes. Studying this phenomenon is complicated by the fact that electroporating cells in common microgravity simulators, such as the rotating wall vessel and the random positioning machine (RPM), is currently not feasible. In this work, we design and validate a custom, electroporation-capable RPM. The device consists of two rotating frames, which continuously reorient a biological sample relative to the direction of gravity, while also allowing for the delivery of intense electric pulses required for electroporation. The confirmation of the RPM's simulation of microgravity was assessed using an accelerometer. Once validated, a proof-of-concept experiment was performed on human T-lymphocytes to assess the effect of microgravity adaptation on membrane permeability following electroporation. Cell permeability after electroporation decreased after simulated microgravity exposure, suggesting that cellular adaptations to microgravity may alter electroporation outcomes.

This study investigated the molecular mechanisms by which ginsenoside Rg3 combined with ranibizumab alleviates diabetic macular edema (DME), focusing on antagonizing ANGPTL4/VEGF and regulating the NRP/RhoA pathway to reduce vascular permeability. Transcriptomic sequencing compared blood samples from DME patients and healthy controls, followed by GO/KEGG enrichment analysis. In vitro, human retinal microvascular endothelial cells (HRMECs) were treated with ginsenoside Rg3 (5, 10, 20 μM) alone or combined with ranibizumab (1 mg/mL); cell viability, permeability, and protein expression were assessed. In vivo, diabetic rats received intraperitoneal ginsenoside Rg3 and ranibizumab; ocular pathology, angiogenesis, inflammation, and key protein expression/activity were evaluated. DME patients exhibited significant upregulation of VEGF, ANGPTL4, NRP1 (logFC = 1.9, P < 0.01), and RhoA, associated with angiogenesis/migration/inflammation pathways. In vitro, 10 μM ginsenoside Rg3 optimally reduced HRMEC permeability and suppressed ANGPTL4. Combination therapy further decreased VEGF and ANGPTL4 expression. In vivo, combined treatment significantly reduced retinal edema, angiogenesis, and vascular permeability. It markedly inhibited NRP1 expression and reduced RhoA/ROCK activity. The combination of ginsenoside Rg3 and ranibizumab effectively antagonizes ANGPTL4 and VEGF and regulates the NRP/RhoA pathway, significantly reducing vascular permeability in DME through synergistic action. This provides crucial theoretical support for novel DME combination therapy.

Nanoemulsions were prepared with a ginsenoside-rich extract (GE), a non-ginsenoside extract (NGE), and their combination to investigate how heterogeneous components influence droplet interfacial properties. All formulations produced nanoscale droplets. TEM revealed compositional differences in morphology, with NGE-containing formulations exhibiting more irregular structures. FALT analysis showed that both GE and NGE increased interfacial layer thickness compared with blank formulations, with NGE producing a greater effect, while the combined GE/NGE nanoemulsion exhibited reduced thickness, suggesting interfacial restructuring. Encapsulation efficiency depended on ginsenoside aglycone type, with PPD-type compounds showing higher incorporation than PPT-type. NGE-containing systems demonstrated improved freeze-thaw and storage stability. During simulated digestion, GE/NGE nanoemulsions exhibited the greatest lipid hydrolysis extent, consistent with altered interfacial organization. Cellular uptake assays showed selective permeability of Rb1 and Rg1, with GE/NGE achieving the highest Rb1 transport and modest downregulation of inflammatory markers. Overall, co-encapsulation modulates interfacial architecture, thereby influencing functional performance.

Cell encapsulation within semipermeable membranes is a promising strategy for protecting transplanted cells from host immune responses, while permitting the diffusion of nutrients and therapeutic molecules. Although alginate-based microcapsules are commonly used, ionically crosslinked capsules often exhibit limited structural stability and tunability in terms of membrane permeability. In this study, we developed covalently stabilized microcapsules. Alginate microgel beads were first prepared as sacrificial templates and subsequently coated with phenol-modified chitosan and hyaluronic acid (Chitosan–Ph and HA-Ph) via layer-by-layer assembly. The multilayer membrane was then covalently stabilized through horseradish peroxidase (HRP)-mediated oxidative coupling of phenol groups, followed by liquefaction of the alginate core. The crosslinked microcapsules maintained structural integrity after liquefaction, while markedly reducing γ-globulin permeation under in vitro conditions and preserving β-cell viability and glucose responsiveness. The findings of this study demonstrate the feasibility of this system as an in vitro platform for stable cell encapsulation, with potential relevance to cell therapy.

Abstract This study presents the development of a hydrogel-supported perfusion platform designed for ex vivo uterine tissue graft cultivation under physiologically relevant conditions. Polyvinyl alcohol/Borax hydrogels were synthesized and systematically characterized by Fourier-transform infrared spectroscopy, rheological measurements, and swelling analyses, confirming the formation of borate–diol crosslinked hydrogel networks arising from reversible interactions characteristic of PVA/Borax systems, together with viscoelastic stability and high water retention capacity. Biocompatibility assays demonstrated that hydrogels maintained at physiological pH preserved cell viability above the ISO 10993-5 threshold, supporting their suitability as a matrix for tissue culture. A permeable nitrocellulose membrane, obtained by chemical modification of onion-derived cellulose, was incorporated into polyvinyl chloride tubing to enable controlled fluid exchange and nutrient transport. Integration of this membrane-modified tubing with the hydrogel scaffold created a perfusion system capable of sustaining uterine grafts in vitro by maintaining pH balance, supporting metabolite clearance, and enabling effective gas diffusion. The system maintained stable perfusion conditions and supported structural preservation of uterine tissue over a 5 d culture period. Preliminary trials with ovine uterine tissues confirmed the feasibility of the platform as a functional ex vivo culture environment. These findings demonstrate that the proposed system provides a physiologically relevant and scalable platform for ex vivo uterine tissue maintenance, with potential applications in reproductive biology, disease modeling, and regenerative medicine.

The article uses a systems approach to study the technologies for combating oil pollution of the environment in China, and provides a detailed examination of the methods for cleaning oil-contaminated soils, ways of cleaning contaminated water bodies, and the oil sorbents used. Semi-permeable membranes, reverse osmosis technologies, and sorption materials are widely used to clean groundwater and underground water from oil pollution. Oil-contaminated soil is cleaned using bioremediation technologies using microorganisms, technologies for physicochemical restoration of soils, and a combination of these methods. The performed analysis made it possible to identify possible ways to improve the technologies for combating oil pollution, which are aimed at reducing costs; reducing the cleaning cycle; the possibility of repeated use of reagents and minimal formation of non-recyclable waste; reducing the risk of secondary pollution; the possibility of combined restoration of contaminated soil and groundwater; optimization of the production of effective and multifunctional materials with a wide range of applications in various environmental conditions; determining the mechanisms of interaction between reagents and sorbents and pollutants; increasing the level of intellectualization and robotization of the equipment used in order to improve the safety of workers cleaning the surface of water and soil from contamination by oil and oil products.

Characterizing drug distribution to target organs is of central importance to drug discovery, especially for compounds intended to reach the central nervous system (CNS). However, the current benchmark standard measurements, based on tissue homogenate, provide limited spatial and temporal resolution. Here, we use real-time electrochemical aptamer-based (E-AB) monitoring to determine drug concentrations across specific brain regions, blood, and liver of rats after intravenous dosing. Using vancomycin and tobramycin as models, we reveal significant regional differences in brain pharmacokinetics. Vancomycin shows distinct kinetics across cortex, hippocampus, and thalamus, crossing the blood-brain barrier (BBB) but showing limited transport across the blood-cerebrospinal fluid barrier (BCSFB). Tobramycin, despite its smaller size, fails to cross either barrier. Vancomycin's liver distribution is delayed and limited, resembling its brain kinetics more than blood. These findings challenge assumptions of uniform CNS drug distribution and fast liver uptake, highlighting the need for spatially and temporally resolved pharmacokinetic assessments. Our approach enables high-resolution, in vivo profiling of drug absorption, distribution, and clearance, offering a powerful tool to inform dosing strategies and improve translational outcomes.

Pathological aggregation of α-synuclein is a hallmark of synucleinopathies such as Parkinson's disease, where fibrillar α-synuclein aggregates drive neurodegeneration. Here, we aimed to identify small molecules capable of disassembling fibrillar α-synuclein aggregates by screening a natural product library using a plasmonic nanoparticle amyloid corona platform. Candidates were further ranked based on key physicochemical properties (molecular weight, solubility, and lipophilicity) associated with cell permeability and potential central nervous system accessibility. Through this analysis, angelic acid emerged as the top candidate. Physicochemical characterization, including circular dichroism, Fourier-transform infrared spectroscopy, transmission electron microscopy, and atomic force microscopy, demonstrated that angelic acid disrupts β-sheet-rich conformations and fragments α-synuclein fibrils. Molecular docking analysis suggested potential interactions of angelic acid with β-sheet interface regions across multiple α-synuclein fibril polymorphs. In a bimolecular fluorescence complementation cell model, angelic acid reduced intracellular α-synuclein accumulation by up to 91.4% at 100 μM. In addition, angelic acid alleviated α-synuclein fibril-induced cytotoxicity by 34.1%, demonstrating both reduced cellular α-synuclein levels and attenuation of α-synuclein fibril-induced cytotoxicity. Collectively, these findings suggest that angelic acid is a pathological α-synuclein-targeting lead compound for synucleinopathies, highlighting the need for further in vivo evaluation in synucleinopathy models.

The typically low, molecule-dependent permeability of antibodies across the blood-brain barrier (BBB) has driven the development of engineered constructs with optimized BBB transcytosis to facilitate efficient brain delivery. Physiologically-based pharmacokinetic (PBPK) modeling provides a framework to predict brain disposition and inform drug development; however, current models lack true a priori predictive capability and remain dependent on in-vivo data. In-vitro brain endothelial cell permeability (Papp) assays provide antibody-specific estimates of brain transport, though these assays have yet to be integrated into PBPK models. This study developed and cross-validated an integrated in-vitro-in-vivo-extrapolation (IVIVE) PBPK framework that uses Papp values to predict antibody-specific cerebrospinal fluid (CSF) concentrations a priori. Seven antibodies were evaluated, including four standard (non-FC5-fused) and three TMEM30A-binding constructs (FC5-fused). PBPK modeling was conducted using PK-Sim®/MoBi®. Papp values were used to estimate antibody-specific brain transport parameters. For comparison, a conventional modeling approach was implemented, where brain transport was inferred to be similar to a reference antibody (trastuzumab). Model performance was assessed by comparing predicted versus observed CSF exposures (area-under-the-concentration-time-curve) in rats following intravenous administration. Integration of Papp data substantially improved brain exposure predictions, reducing the absolute average percentage prediction error for CSF exposure from 296.1% (conventional approach) to 53.4% (IVIVE-PBPK). The framework accurately captured the brain disposition of both standard and FC5-fused antibodies without requiring pre-existing in-vivo CSF data. Overall, this Papp-informed PBPKmodeling approach enables a priori, mechanistic prediction of antibody brain exposure, supporting candidate selection and reducing reliance on animal studies in brain drug development.