Bacterial infection at the surface of oral implants is one of the primary reasons for surgical failure. To counter the risk of biofilm infection on oral implants and prevent the emergence of drug-resistant bacteria, an increasing number of researchers are focusing on the study of surface coatings for oral implants. Therefore, an antibacterial hydrophilic coating was developed in this study. This coating combines a biomimetic adhesive (dopamine-modified oxidized hyaluronic acid) with a long-acting drug-loaded carrier (aminated mesoporous silica particles) on a polyurethane material through electrostatic self-assembly and a Schiff base reaction. The results showed that the drug-loaded mesoporous silica nanoparticles prepared by the solvent template method had a diameter of approximately 200 nm and a pore size of about 3 nm. The drug could be continuously released in vitro for more than 9 days. Dopamine-modified hyaluronic acid can firmly adhere the drug-loaded mesoporous silica nanoparticles to the material surface, forming a uniform and stable coating. Additionally, the composite coating exhibited effective antibacterial properties against S. aureus and E. coli. The CCK-8 and fluorescence staining results showed that the coating had excellent biocompatibility.

The persistent threat of phytopathogenic fungi necessitates precision-targeted and sustainable antifungal strategies beyond conventional agrochemicals. This study presents a hierarchically structured micro/nanosystem (CMC@Eu-ZIF@ZnO) engineered for precision antifungal delivery by leveraging the specific virulence mechanisms of Botrytis cinerea. The composite features a dual core-shell architecture: a ZnO microsphere core encapsulated within a ZIF-8 intermediate shell and an outer carboxymethyl cellulose (CMC) coating. This intelligent design integrates pH- and cellulase-triggered release pathways, exploiting fungal-induced and enzymatic secretion for on-demand cargo delivery. Synergistic action between Eu and ZnO nanoparticles enhances membrane disruption and oxidative stress, resulting in superior antifungal activity. The system achieved 91.5 % cumulative release under dual stimuli and 67.9 % rainfast retention, with negligible phytotoxicity in soybean germination assays and effective lesion control in tomato leaves. By overcoming instability, non-target leakage, and limited responsiveness of conventional fungicides, this study establishes a microenvironment-responsive hierarchical delivery platform. This work highlights the potential of integrating natural antifungals with hierarchical nanostructures for eco-friendly, precision crop protection.

The encapsulation of lipophilic compounds for use in the cosmetic, food, and detergency industries is an area of growing interest. However, most current strategies rely on non-biodegradable materials, often classified as microplastics, which pose significant environmental risks. To address these issues, alternative encapsulation methods using biodegradable materials are being developed. Despite their potential, these methods have yet to demonstrate efficacy or economic feasibility comparable to conventional encapsulation systems. To overcome these challenges, a novel strategy has been developed for the encapsulation of lipophilic compounds, such as fragrances, using sodium alginate (SA). This approach involves the formation of an oil-in-water nanoemulsion via the Phase Inversion Composition method, with polysorbate 80 serving as the surfactant. The process is followed by the internal gelation of SA and subsequent dispersion to generate the final microcapsules. The formulation was optimized by varying the ratios of surfactant, oil, and aqueous phases in the nanoemulsion. Characterization techniques, including Dynamic Light Scattering, Gas Chromatography-Mass Spectrometry, and Thermogravimetric Analysis, confirmed successful encapsulation (average of 81 %, up to 97 % for one fragrance). The formulations demonstrated prolonged release profiles, with the scent remaining detectable for up to 30 days. An organoleptic study further revealed that encapsulated fragrances retained higher perceived intensity over time compared to their non-encapsulated counterparts. Moreover, the microcapsules exhibited excellent long-term stability within a conditioner matrix, maintaining their fragrance load for four months. This work represents a significant advancement in the development of environmentally friendly encapsulation methods for lipophilic compounds, offering promising applications in the cosmetic industry.

The course of the skull defect is long, with multiple factors involved. Traditional treatment methods are not sufficient to completely restore the skull defect in a short period. Biomaterial scaffold could replace traditional approaches to bone reconstruction. A major challenge in designing a scaffold for cranial defect repair is to be non-toxic, low swelling, biodegradable, and pro-osteogenic. Herein, a biodegradable aerogel scaffold composed of methylcellulose (MC), thiolated chitosan (TCS), Zn and nano hydroxyapatite (nHA) was designed for repairing the skull defect. MC/TCS-nHA aerogel was formed by the ionic cross-linking of hydroxyl, amino and thiol groups with Zn. The prepared scaffolds exhibited a uniform pore structure and structural stability. Interestingly, TCS was used to enhance biocompatibility and biodegradability, Zn to enhance antibacterial properties and nHA to enhance pro-osteogenicity. In vivo and in vitro tests confirmed that chitosan-based aerogel could promote macrophage polarization into the M2 phenotype and promote angiogenesis and osteogenesis. The micro-CT characterization analysis and immunofluorescence analysis after 12 weeks indicated that MC/TCS-nHA aerogel could accelerate skull defect repair. Therefore, the chitosan-based aerogel showed great promise as an implant material for medical applications involving the repair of the skull.

Thrombosis persists as the primary cause of life-threatening cardiovascular disorders globally. The inability of drugs to accurately locate the disease site and short blood circulation time are the main reasons affecting thrombus treatment. To improve treatment efficacy, a targeted antithrombotic strategy has been developed to specifically deliver drugs to thrombotic sites. The platelet membrane-camouflaged magnetic nanoformulations have been fabricated as a dual-targeting nanocarrier for co-delivery the thrombolytic agent urokinase (UK) and the anticoagulant tirofiban (TF). The nanoformulations were created by encapsulating the drugs within magnetic mesoporous silica (MMS), followed by coating with polydopamine (PDA) and a platelet membranes (PMs) to form the final composite, referred to as TU-MMS@PP. The PMs coating enhances biocompatibility, prolongs circulation time in vivo, and extends the half-life of the loaded drugs. Additionally, the PMs camouflage provides the nanoparticles with "stealth" properties, allowing them to evade immune detection and clearance, thereby improving targeted delivery to thrombus sites and enhancing thrombolytic efficiency. In vivo studies confirmed that the TU-MMS@PP nanoformulations could rapidly restore blood flow at thrombosed sites within 30 min, demonstrating their potential as an effective antithrombotic therapy.

The performance of nanoparticle-based biosensors strongly depends on the orientation and density of immobilized antibodies, yet these parameters remain underexplored in platforms based on dynamic light scattering (DLS). This study investigates how the length of molecular crosslinkers influences antibody orientation, surface coverage, and biosensor sensitivity for SARS-CoV-2 detection. The impact of crosslinker spacer length on the analytical performance of 53 nm-gold nanoparticles (AuNPs) functionalized with polyclonal antibodies (pAb) was evaluated using both the spike protein (S Ptn) and intact viral particles as targets. Biosensors were prepared using carboxylic acid-terminated alkanethiol crosslinkers of varying lengths-3-mercaptopropionic acid (MPA), 6-mercaptohexanoic acid (MHA), and 11-mercaptoundecanoic acid (MUA)-and characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy. DLS was used to monitor changes in hydrodynamic diameter (ΔD) upon antigen binding in artificial saliva. Secondary structure analysis and mathematical fitting using the Hill model were employed to evaluate structural effects and binding cooperativity. MUA-functionalized biosensors showed the best performance, with ΔD shifts up to 115.2 nm for the S Ptn and 77.76 nm for the virus, with respective limits of detection of 2.96 ng/mL and 1.8 × 10 ³ PFU/mL. These improvements were associated with increased antibody packing and favorable end-on orientation. A Hill coefficient of 2.82 in virus detection indicated positively cooperative binding behavior. This study enhances our understanding of antibody-antigen interactions on nanostructured surfaces and guides the development of more effective DLS-based biosensors.

Plant proteins exhibit wide variability in emulsifying behavior due to differences in composition, molecular structure, and processing history. This study investigated the relationship between intrinsic physicochemical properties and emulsifying behavior of eleven commercial protein isolates and concentrates derived from bovine milk, soy, canola, faba bean and pea. Key properties including solubility, surface hydrophobicity (SH), molecular weight distribution (MWD), and zeta-potential of the protein ingredients were characterized and evaluated in relation to emulsion droplet size. Among these parameters, MWD showed a moderate correlation with emulsion droplet size (R² = 0.64), while SH and zeta potential exhibited no meaningful correlation (R² < 0.1). When MWD and SH were evaluated together, a clearer trend and separation emerged. Plant proteins with both high molecular weight and low surface hydrophobicity showed a tendency to form heavily flocculated emulsions. This flocculation likely resulted from slower interfacial adsorption and incomplete surface coverage, leading to droplet flocculation at early stages of emulsification. Under a specific set of formulation and processing conditions, emulsions prepared with alkaline-extracted pea and faba protein had smaller droplet size than their air-classified counterparts, likely due to their lower MWD and modified interfacial behavior induced by alkaline treatment. These findings show that the combination of MWD and SH could be useful in understanding the emulsifying behavior of commercial plant protein ingredients and helping in the screening and formulation of plant protein ingredients for food and beverage applications.

Anticoagulant therapy substantially increases the risk of post-extraction hemorrhage by impairing hemostasis. In this study, we designed a quaternized carboxymethyl chitosan/polydopamine composite hemostatic sponge (QCD) that combines mechanical robustness and biocompatibility. Compared with the Gel group, QCD exhibits markedly enhanced in vitro hemostatic and antibacterial performance; the quaternary ammonium modification confers potent antibacterial activity tailored to the complex oral environment and mitigates infection risk. In vivo, tooth extraction test in anticoagulated rats showed that QCD (blood loss 0.011 ± 0.001 g, hemostasis time 59.667 ± 4.163 s) significantly outperformed a commercial gelatin sponge (0.019 ± 0.001 g, 87.000 ± 4.082 s) in hemostasis. This superiority was attributable to its rapid blood absorption and enhanced adhesion of blood cells and platelets, which together promoted clot formation. These results suggest that QCD may serve as a practical and promising approach for managing post-extraction hemorrhage in anticoagulated patients.

The purpose of this study was to design and fabricate hepatocyte and mitochondria dual-targeted nanoparticles for improving the stability and utilization of procyanidins (PC). PC nanoparticles were prepared by emulsion solvent evaporation method using (5-carboxypentyl) (triphenyl) phosphonium bromide modified PC as core materials, lactobionic acid and 3-amino phenylboronic acid modified hyaluronic acid as wall materials. The obtained nanoparticles were spherical, with small size, high encapsulation efficiency (> 80 %) and strong antioxidant capacity. Compared with free PC, the stability of loaded PC was improved under high temperature, UV radiation, long-term storage, freeze-thaw cycles, simulated digestion and other conditions. In vitro studies proved that nanoparticles had reactive oxygen species-responsive, hepatocyte and mitochondria dual targeting functional properties. In addition, dual-targeted PC nanoparticles could also inhibit the elevation of intracellular reactive oxygen species level and the decrease of mitochondrial membrane potential caused by high-fat. This work proposes a new strategy to deliver active compounds to hepatocytes and even mitochondria, which can provide new ideas for nutritional interventions in liver-related chronic diseases induced by high-fat diets.

Human pluripotent stem cell (hPSC)-derived induced mesenchymal stem cells (iMSCs) offer advantages over tissue-derived MSCs in their in unlimited expansion, minimal batch-to-batch variation, controllable pathogen status, and large-scale production potential. Yet traditional iMSC differentiation methods face limitations that necessitate a more efficient approach. Based on the classic TGF-β inhibitor (SB431542) induction system, this study established a three-stage iMSC differentiation method: 10-day Laminin-521/Gelatin induction, 11-day screening on 0.1 % gelatin-coated dishes (enriching precursors via differential cell-gelatin adhesion), and 3-5-day amplification. A xeno-free system was established. Flow cytometry, trilineage differentiation, RNA sequencing, karyotype analysis, and nude mouse tumorigenicity tests validated iMSC quality. This straightforward, cost-effective method (≈￥2000-3000 for 1 ×10⁸ P0 iMSCs) yields high-purity iMSCs with strong proliferation, tissue-derived MSC-like transcriptomes, and enhanced bone repair capacity in a mouse femoral fracture model. It also further implicates the gelatin DGEA motif (which mimics gelatin's effect) as key for iMSC differentiation, addressing classical iMSC industrialization issues and informing clinical translation.

Currently, the groundbreaking progress of immune checkpoint inhibitors has benefited patients with various types of tumors. However, the efficacy of these inhibitors is constrained by the tumor immune-suppressive microenvironment. Furthermore, the hypoxia mediated by intratumoral vascular compression further weakens the anti-tumor immune response within the tumor. Herein, we have meticulously developed a drug-sustained-release scaffold that contains three drug components of oxaliplatin, losartan, and immune checkpoint inhibitor (anti-PD-L1), structured with a thermosensitive hydrogel F127 that can gel in situ upon triggering at body temperature. Oxaliplatin, an effective chemotherapeutic agent, can induce immunogenic cell death in tumor, effectively alleviating the tumor immune-suppressive microenvironment. Meanwhile, losartan potassium, a clinical antihypertensive drug, can reduce tumor stroma, lower tumor solid stress, and relieve intratumoral vascular compression, thereby improving tumor hypoxia. The anti-PD-L1 is a widely used immune checkpoint inhibitor and can precisely block the binding of PD-L1 to PD-1, activating T cell-mediated anti-tumor immune responses. The constructed F127@Oxpt-Los-aPDL1 scaffold triggers a potent anti-tumor immune response, achieving outstanding tumor suppression effects and even induces a powerful abscopal effect, effectively inhibiting the growth of distant tumors. This research presents a novel combination treatment strategy aimed at enhancing the efficacy of immune checkpoint inhibition therapy in stroma-rich tumors.

Oral squamous cell carcinoma (OSCC) remains a major global health problem due to its aggressive nature and the limitations of conventional chemotherapy, including poor drug specificity and severe systemic toxicity. To address this challenge, in the present study we have designed a smart, injectable hydrogel with dual responsiveness (pH and temperature) enabling to reduce the tumor growth. The hydrogel was fabricated by crosslinking sodium alginate (SA) with calcium ions and integrating poly (N-isopropylacrylamide) grafted dextran (dx) (PNIPAM-g-dx), and loaded with doxorubicin (Dox) resulting in a multi-stimuli responsive network named DSPD-Hg. This fabricated hydrogel maintains structural integrity under physiological conditions but exhibited enhanced drug release in acidic and hyperthermic tumour settings, particularly under NIR irradiation. The in vitro and in vivo evaluations reveal that DSPD-Hg facilitates sustained Dox release, significantly enhances tumour inhibition through combined chemotherapeutic and photothermal effects, and demonstrates excellent biocompatibility. Prominently, the hydrogel was found to be biocompatible and accumulated preferentially at the tumor site, minimizing harm to healthy tissue. Our findings suggest that DSPD-Hg smart hydrogel system offers a promising, targeted, and less toxic alternative for the treatment of OSCC.

This study investigates the molecular interactions of the antiviral agent oseltamivir phosphate (OSL) with a two-dimensional (2D) Langmuir monolayer model of the influenza A (AH1N1) virus lipid envelope. Targeting the viral lipid envelope, which predominantly contains phosphatidylethanolamines (PE), sphingomyelin (SM), and phosphatidylserines (PS) in the AH1N1 strain, is considered an alternative strategy for developing novel antivirals. The model consists of a ternary lipid mixture (DOPE:DMPS:SM 50:35:15), prepared at the air-water interface and characterized using surface-sensitive techniques including Brewster angle microscopy (BAM), grazing incidence X-ray diffraction (GIXD), and polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). OSL incorporation significantly disorganizes the ternary membrane, causing concentration-dependent shifts in surface pressure-area per molecule (π-A) isotherms toward larger areas. OSL reduces the maximum value of compression modulus (Cs), resulting in a much less organized layer. Analysis of thermodynamic functions obtained from the compression-expansion cycles confirmed reduction of attractive intermolecular interactions, thereby preventing the formation of irreversible assemblies. Studies using single-component monolayers revealed that OSL-lipid interactions were electrostatic-dependent: OSL had minimal impact on neutral DOPE and SM monolayers, but showed significant concentration-dependent influence on the negatively charged DMPS monolayer. For DMPS, OSL induces fluidization, confirmed by PM-IRRAS observations of hydrogen bonding in the headgroup region and shifts in acyl chain bands to higher wavenumbers, indicative of a less ordered conformation. BAM and GIXD studies further demonstrated that OSL hinders the formation of condensed DMPS domains. These findings are crucial for understanding antiviral-lipid envelope mechanisms and designing novel targeted therapies.

Pathogenic food microbes pose a serious threat to global health, leading to widespread disease outbreaks, economic losses, and disruptions in the food processing and distribution chain. Current detection methods for infectious agents, including conventional culturing and genotypic techniques, are accurate but often face limitations such as costly equipment, the need for specialized personnel, and lengthy analysis times. Hyperspectral imaging (HSI) has emerged as a promising alternative that provides a fast, non-invasive, and high-throughput approach for early identification of pathogenic food microbes. HSI combines spatial and spectral characterization to deliver information across a broad wavelength range. This technology enables the recognition and identification of microbial agents by analyzing their unique spectral fingerprints, which reflect the biochemical and physical properties of bacteria, fungi, and viruses in various food matrices, including raw produce, animal protein, and milk-based foods. A typical HSI system can acquire a complete spectral cube in less than a minute per sample, capturing 100-300 contiguous spectral bands across the visible to near-infrared range, thus enabling rapid and comprehensive microbial screening. This review highlights several foodborne pathogens and the strong applicability of HSI for their identification. Additionally, it discusses recent trends, suggests future directions, and emphasizes AI adoption along with the development of portable HSI devices for on-site food safety assessment.

M2 tumor-associated macrophages (TAMs) can promote metastasis of triple-negative breast cancer (TNBC). TNBC cells release exosomes to exchange information. By doing so, they reprogram the phenotype of TAMs. TRAF3IP2 is a key factor mediating the metastasis and is highly expressed in TNBC; however, it is still unclear whether it has an impact on TAMs. This study explored the mechanism of the interaction between TNBC and TAMs, and evaluated a novel nanotherapy strategy to intervene in this process.

Exosomes, endogenous nanoscale vesicles secreted by various cell types, have emerged as promising natural carriers for therapeutic delivery due to their excellent biocompatibility, low immunogenicity, prolonged systemic circulation, and intrinsic ability to cross the blood-brain barrier (BBB). They can encapsulate diverse bioactive molecules-including nucleic acids, proteins, and small-molecule drugs-showing great potential in cancer therapy. However, their clinical translation remains hindered by low production yield and limited drug-loading capacity. To overcome these limitations, engineered approaches such as exosome-liposome fusion have been developed. This strategy integrates the biological targeting and membrane stability of exosomes with the tunable physicochemical properties of liposomes, resulting in hybrid exosome-liposome nanoparticles (HELNs) that exhibit improved stability, loading efficiency, and therapeutic performance. This review systematically summarizes the biological characteristics of exosomes from different cellular origins, current methodologies for HELNs fabrication, and their recent advances in drug delivery, gene therapy, and immunotherapy. Finally, the review highlights key advantages of this hybrid strategy for cancer theranostics and discusses ongoing challenges and future perspectives for large-scale production and clinical translation.

Research on the surface properties of lactic acid bacteria (LAB) has traditionally emphasized isolated measurements, while systematic studies that correlative analysis of multiple surface properties relate these features to one another are still limited. The aim of this study was to provide the first integrated investigation of Lactobacillus surface chemistry by combining comprehensive molecular profiling with multi-technique physicochemical validation to achieve a systematic characterization of LAB surface properties. An initial screening of 42 Lactobacillus strains based on zeta potential and hydrophobicity led to the selection of eight representative strains for in-depth analysis. Fourier Transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) revealed that the most hydrophobic and hydrophilic strains, L. acidophilus ATCC4356 (1-1) and L. helveticus AG10-1 (8-8), exhibited the highest N/C (0.134) and O/C (0.530) ratios, indicating protein-rich and polysaccharide-dominant surfaces, respectively. Water contact angles (58.7°-100.4°) in contact angle measurement (CAM) were closely aligned with hydrophobicity levels determined by microbial adhesion to solvents (MATS), ranging from 4.61 % to 64.42 %. MATS and CAM agreed on hydrophobicity but diverged sharply in their assessment of Lewis acid-base (AB) properties (R² < 0.20). Highly hydrophobic strains, lacking steric hindrance from hydrophilic polysaccharides, exhibited overall greater autoaggregation, though this behavior was also moderately influenced by zeta potential providing electrostatic repulsion between cells. These findings provide new insight into the molecular basis of Lactobacillus surface functionality and emphasize the importance of multi-method strategies for selecting and characterizing strains for probiotic development and biointerface applications.

Serous ovarian carcinoma (SOC) is distinguished by marked invasiveness, early dissemination and rapid drug resistance, creating an urgent demand for non‑cross‑resistant alternative therapies. Consequently, the exploration of minimally invasive yet highly effective treatment modalities has become a central research priority. In the present work, a heterobimetallic metal-organic frameworks (MOFs) sonosensitizer, namely Mn‑MX@MIL‑125(Ti), was synthesized by introducing manganese(II) ions into MXene-trussed Ti‑based organic frameworks. The obtained Mn-MX@MIL-125(Ti) exhibited high specific surface area, tunable mesoporous, and abundant metal sites, which collectively conferred excellent catalytic activity. Through a series of tests, it was found that Mn‑MX@MIL‑125(Ti) enhanced the generation of reactive oxygen species (ROS) under low‑intensity ultrasound. For the SK-OV-3 cells, the PEG ylated Mn-MX@MIL-125(Ti) displayed good biocompatibility, but upon ultrasound irradiation, it accomplished half‑maximal inhibitory concentration (IC₅₀) of 27.5 µg mL⁻¹ . And, the pronounced decline in mitochondrial membrane potential indicated that it was the ROS‑mediated mitochondrial damage to effectively curtail tumour proliferation. Besides, in subcutaneous SOC murine model, the tumour‑inhibition rate of 83 % was achieved without discernible systemic toxicity. These results highlight that the Mn-MX@MIL-125(Ti) as a promising bimetallic sonosensitizer is capable of efficiently suppressing the SOC via ultrasound-induced ROS generation.

Tauopathies, containing aging-related Alzheimer's disease (AD) and contact sports-related chronic traumatic encephalopathy (CTE), etc., are neuropathologically characteristic of the tau protein aggregates in the brain. Targeting the oligomeric species formed in the route of tau fibrilization has been considered a promising therapeutic approach to prevent or treat tauopathies. In vitro experiment reported that S305 phosphorylation (Pho-S305) exerted a protective role in tau aggregation. However, the atomic effect and molecular mechanisms of Pho-S305 on tau aggregation are largely elusive. In this study, we performed replica exchange molecular dynamics (REMD) and classical molecular dynamics (MD) simulations, with a total simulation time of 57 μs, on tau peptides without and with Pho-S305. The protein model was a novel tau fragment (G302-S316), constituting the ordered core of a first intermediate amyloid (FIA) filament of AD- and CTE-specific tau filament. The REMD results revealed that Pho-S305 suppressed the β-sheet formation and weakened the peptide-peptide interaction, thus inhibiting the aggregation of the peptides. Additional MD simulations indicated that the oligomerization dynamics of the peptides were disturbed by Pho-S305. Our findings excavate the mechanistic information underlying the phosphorylation-induced inhibitive effects on tau aggregation, which may provide potential useful clues for the development of therapeutic avenues for tauopathies.

Microfibrillated silk (MFS) is an emerging class of silk materials produced by directly exfoliating silk fibres, offering a top-down alternative to traditional regenerated silk processing methods. They have the potential to be used as biomaterials, particularly in tissue engineering and regenerative medicine. This study used a unique tuneable top-down approach to produce different MFS suspensions. These were then fabricated into protein papers using two scalable methods, casting and vacuum filtration, to examine how processing and fabrication together influenced the final material properties and associated cellular responses. MFS suspensions were prepared under three processing levels using mechanical processing alone or combined with acid pre-treatment with each level yielding increasingly finer fibrils. The level of fibrillation significantly affected fibre morphology and mechanical strength, while the fabrication method mainly influenced surface roughness and bilayer characteristics. Papers made with mechanical processing alone had the highest strength. Cast papers revealed a surface difference, with a rough top surface and smooth bottom surface, while vacuum-filtered papers had uniform roughness on both sides. These surface differences, along with the degree of fibrillation, impacted cell attachment and organization, with cast papers from acid-pretreated and shear-homogenised MFS showing the best biological outcomes. Controlling MFS processing and assembly techniques to form papers enables the design of silk-based materials tailored for various biomedical applications.