F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

Bioprinting of human dermal microtissues precursors as building blocks for endogenousin vitroconnective tissue manufacturing.

The advent of 3D bioprinting technologies in tissue engineering has unlocked the potential to fabricatein vitrotissue models, overcoming the constraints associated with the shape limitations of preformed scaffolds. However, achieving an accurate mimicry of complex tissue microenvironments, encompassing cellular and biochemical components, and orchestrating their supramolecular assembly to form hierarchical structures while maintaining control over tissue formation, is crucial for gaining deeper insights into tissue repair and regeneration. Building upon our expertise in developing competent three-dimensional tissue equivalents (e.g. skin, gut, cervix), we established a two-step bottom-up approach involving the dynamic assembly of microtissue precursors (µTPs) to generate macroscopic functional tissue composed of cell-secreted extracellular matrix (ECM). To enhance precision and scalability, we integrated extrusion-based bioprinting technology into our established paradigm to automate, control and guide the coherent assembly ofµTPs into predefined shapes. Compared to cell-aggregated bioink, ourµTPs represent a functional unit where cells are embedded in their specific ECM.µTPs were derived from human dermal fibroblasts dynamically seeded onto gelatin-based microbeads. After 9 days,µTPs were suspended (50% v/v) in Pluronic-F127 (30% w/v) (µTP:P30), and the obtained formulation was loaded as bioink into the syringe of the Dr.INVIVO-4D6 extrusion based bioprinter.µTP:P30 bioink showed shear-thinning behavior and temperature-dependent viscosity (gel atT> 30 °C), ensuringµTPs homogenous dispersion within the gel and optimal printability. The bioprinting involved extruding several geometries (line, circle, and square) into Pluronic-F127 (40% w/v) (P40) support bath, leveraging its shear-recovery property. P40 effectively held the bioink throughout and after the bioprinting procedure, untilµTPs fused into a continuous connective tissue.µTPs fusion dynamics was studied over 8 days of culture, while the resulting endogenous construct underwent 28 days culture. Histological, immunofluorescence analysis, and second harmonic generation reconstruction revealed an increase in endogenous collagen and fibronectin production within the bioprinted construct, closely resembling the composition of the native connective tissues.

Sleep deprivation boosts O2·- levels in the brains of mice as visualized by a Golgi apparatus-targeted ratiometric fluorescence nanosensor.

Sleep deprivation (SD) is highly prevalent in the modern technological world. Emerging evidence shows that sleep deprivation is associated with oxidative stress. At the organelle level, the Golgi apparatus actively participates in the stress response. In this study, to determine whether SD and Golgi apparatus stress are correlated, we rationally designed and fabricated a novel Golgi apparatus-targeted ratiometric nanoprobe called Golgi dots for O2·- detection. This probe exhibits high sensitivity and selectivity in cells and brain slices of sleep-deprived mice. Golgi dots can be readily synthesized by coprecipitation of Golgi-F127, an amphiphilic polymer F127 modified with a Golgi apparatus targeting moiety, caffeic acid (CA), the responsive unit for O2·-, and red emissive carbon nanodots (CDs), which act as the reference signal. The fluorescence emission spectrum of the developed nanoprobe showed an intense peak at 674 nm, accompanied by a shoulder peak at 485 nm. As O2·- was gradually added, the fluorescence at 485 nm continuously increased; in contrast, the emission intensity at 674 nm assigned to the CDs remained constant, resulting in the ratiometric sensing of O2·-. The present ratiometric nanoprobe showed high selectivity for O2·- monitoring due to the specific recognition of O2·- by CA. Moreover, the Golgi dots exhibited good linearity with respect to the O2·- concentration within 5 to 40 µM, and the limit of detection (LOD) was ~ 0.13 µM. Additionally, the Golgi dots showed low cytotoxicity and an ability to target the Golgi apparatus. Inspired by these excellent properties, we then applied the Golgi dots to successfully monitor exogenous and endogenous O2·- levels within the Golgi apparatus. Importantly, with the help of Golgi dots, we determined that SD substantially elevated O2·- levels in the brain.

A Novel growth guidance system for early onset scoliosis: a preliminary in vitro study.

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.

Utilization of Nitrogen-Doped Graphene Quantum Dots to Neutralize ROS and Modulate Intracellular Antioxidant Pathways to Improve Dry Eye Disease Therapy.

Purpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED. Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice. Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 µg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels. Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.

Investigating cationic and zwitterionic successive multiple ionic-polymer layer coatings for protein separation by capillary electrophoresis.

Successive multiple ionic-polymer layers (SMILs) have long since proved their worth in capillary electrophoresis as they ensure stable electroosmotic flow (EOF) and relatively high separation efficiency. Recently, we demonstrated that plotting the plate height (H) against the solute migration velocity (u) enabled a reliable quantitative evaluation of the coating performances in terms of separation efficiency. In this work, various physicochemical and chemical parameters of the SMIL coating were studied and optimized in order to decrease the slope of the ascending part of the H vs u curve, which is known to be controlled by the homogeneity in charge of the coating surface and by the possible residual solute adsorption onto the coating surface. SMILs based on poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium styrene sulfonate) (PSS) were formed and the effect of each polyelectrolyte molar mass and of the number of polyelectrolyte layers (up to 21 layers) was studied. The use of polyethylene imine as an anchoring first layer was considered. More polyelectrolyte couples based on PDADMAC, polybrene, PSS, poly(vinyl sulfate), and poly(acrylic acid) were tested. Finally, zwitterionic polymers based on the poly(α-l-lysine) scaffold were synthesized and used as the last layer of SMILs, illustrating their ability to finetune the EOF, while maintaining good separation efficiency.

Mass quantification of nanoplastics at wastewater treatment plants by pyrolysis-gas chromatography-mass spectrometry.

Municipal wastewater treatment plants (WWTPs) play a crucial role in the collection and redistribution of plastic particles from both households and industries, contributing to their presence in the environment. Previous studies investigating the levels of plastics in WWTPs, and their removal rates have primarily focused on polymer type, size, shape, colour, and particle count, while comprehensive understanding of the mass concentration of plastic particles, particularly those <1 µm (nanoplastics), remains unclear and lacking. In this study, pyrolysis gas chromatography-mass spectrometry was used to simultaneously determine the mass concentration of nine selected polymers (i.e., polyethylene (PE), polypropylene (PP), polystyrene (PS), poly(ethylene terephthalate) (PET), nylon 6, nylon 66, polyvinylchloride (PVC), poly(methyl methacrylate) (PMMA) and polycarbonate (PC)) below 1 µm in size across the treatment processes or stages of three WWTPs in Australia. All the targeted nanoplastics were detected at concentrations between 0.04 and 7.3 µg/L. Nylon 66 (0.2-7.3 µg/L), PE (0.1-6.6 µg/L), PP (0.1-4.5 µg/L), Nylon 6 (0.1-3.6 µg/L) and PET (0.1-2.2 µg/L), were the predominant polymers in the samples. The mass concentration of the total nanoplastics decreased from 27.7, 18 and 9.1 µg/L in the influent to 1, 1.4 and 0.8 µg/L in the effluent, with approximate removal rates of 96 %, 92 % and 91 % in plants A, B and C, respectively. Based on annual wastewater effluent discharge, it is estimated that approximately 24, 2 and 0.7 kg of nanoplastics are released into the environment per year for WWTPs A, B and C, respectively. This study investigated the mass concentrations and removal rates of nanoplastics with a size range of 0.01-1 µm in wastewater, providing important insight into the pollution levels and distribution patterns of nanoplastics in Australian WWTPs.

Statistical analysis of VEXLPE wear against alumina produced by a new 200-station, multidirectional pin-on-disk device.

With low wear rates shown by contemporary bearing materials of total hip prostheses, the standard deviation of wear rate is relatively high. Therefore, large sample sizes are needed for an adequate power of test. Because wear tests take a long time, it is practical to test several samples simultaneously. A new high-capacity, multidirectional wear test device, called the SuperCTPOD-200, was introduced. A 3 million-cycle wear test with an unprecedented sample size of 200 was performed for VEXLPE. The duration of the test was 6 weeks. The wear factor was normally distributed with a mean ± SD of 1.64 × 10-7 mm3/Nm ± 0.22 × 10-7 mm3/Nm (n = 200). The observation that SD was 13.1% of the mean can be useful in power analyses of future tests with other highly cross-linked polyethylenes. Burnishing was the most typical feature on the worn pins, which was in agreement with clinical findings on retrieved acetabular liners. The present study emphasizes statistics that often plays a minor role only in wear studies.

The influence of polyimide MP-1™ wear particles on a rodent closed fracture healing model.

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats (n = 25) for 1, 3 and 6 weeks. Endpoints included radiography, micro-computed tomography, mechanical testing and paraffin histology. No adverse effects from the wear particles were observed from the current study based on radiology, mechanical or histological data. Although the particles were present, histological analysis revealed a progression in healing between the Polyimide treated groups and the non-treated saline control groups over the duration of 1, 3, and 6 weeks, with no inhibition from the particles. The MP-1™ wear debris generated are larger than 1 µm thus are not able to be engulfed by macrophages and cause osteolysis. This family of polymers (polyimides) may be an ideal material to consider for articulating joints and other implants in the human body.

Irradiation Behavior of Analgesic and Nonsteroidal Anti-Inflammatory Drug-Loaded UHMWPE for Joint Replacement.

Local delivery of pain medication can be a beneficial strategy to address pain management after joint replacement, as it can decrease systemic opioid usage, leading to less side and long-term effects. In this study, we used ultrahigh molecular weight polyethylene (UHMWPE), commonly employed as a bearing material for joint implants, to deliver a wide set of analgesics and the nonsteroidal anti-inflammatory drug tolfenamic acid. We blended the drugs with UHMWPE and processed the blend by compression molding and sterilization by low-dose gamma irradiation. We studied the chemical stability of the eluted drugs, drug elution, tensile properties, and wear resistance of the polymer blends before and after sterilization. The incorporation of bupivacaine hydrochloride and tolfenamic acid in UHMWPE resulted in either single- or dual-drug loaded materials that can be sterilized by gamma irradiation. These compositions were found to be promising for the development of clinically relevant drug-eluting implants for joint replacement.

Sorption properties of pristine and functionalized magnetic carbon nanotubes in relation to double-stranded DNA.

BACKGROUND: Owing to improvement of the molecular diagnostic methods using purified preparations of nucleic acids (NAs), the development of effective methods providing the isolation of DNA is still relevant. The sorption properties of magnetic multi-walled carbon nanotubes (MWCNTs), oxidized MWCNTs and MWCNTs (pristine and oxidized) modified with polydiallyldimethylammonium chloride (pDADMAC) with respect to double strained DNA have been studied. RESULTS: It was shown that in the presence of MWCNTs/pDADMAC particles the DNA molecules were reversibly retained by the particle's surface. The optimal conditions for each step of DNA extraction from model solutions using the obtained material were selected. A comparative evaluation of the effectiveness of the proposed method for DNA isolation based on the results of spectrophotometry and real-time PCR was carried out. It was shown that the desorbed DNA was efficiently amplified in PCR, inhibition of polymerase did not occurred. Probable mechanisms of DNA retention due to the influence of residual impurities of catalysts in the MWCNT composition, as well as the surface charge of nanotubes are proposed. CONCLUSION: Sequentially oxidized and coated with pDADMAC magnetically susceptible CNTs are seemed to be a promising material for development of low-cost systems proving an easy isolation, storage, and subsequent use of dsDNA in molecular diagnostics. The sorption properties of such systems are determined with highly developed specific surface area and their chemical composition.

Structural and therapeutic properties of salicylic acid-solubilized Pluronic solutions and hydrogels.

Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.

Size-based characterization of dendrigraft poly(L-lysine) by free solution capillary electrophoresis using polyelectrolyte multilayer coatings.

Dendrigraft poly(L-lysine) (DGL) constitutes a promising dendritic-like drug vehicle with high biocompatibility and straightforward access via ring-opening polymerization of N-carboxyanhydride in water. The characterization of the different generations of DGL is however challenging due to their heterogeneity in molar mass and branching ratio. In this work, free solution capillary electrophoresis was used to perform selective separation of the three first generations of DGL, and optimized conditions were developed to maximize inter-generation resolution. To reduce solute adsorption on the capillary wall, successive multiple ionic polymer layer coatings terminated with a polycation were deposited onto the inner wall surface. PEGylated polycation was also used as the last layer for the control of the electroosmotic flow (EOF), depending on the PEGylation degree and the methyl-polyethylene glycol (mPEG) chain length. 1 kDa mPEG chains and low grafting densities were found to be the best experimental conditions for a fine tuning of the EOF leading to high peak resolution. Molar mass polydispersity and polydispersity in effective electrophoretic mobility were successfully determined for the three first generations of DGL.

Electrospun zein nanofibers loaded with curcumin as a wound dressing: enhancing properties with PSS and PDADMAC layers.

Development of wound dressings with enhanced therapeutic properties is of great interest in the modern healthcare. In this study, a zein-based nanofibrous wound dressing containing curcumin as a therapeutic agent was fabricated through electrospinning technique. In order to achieve desirable properties, such as antibacterial characteristics, reduced contact angle, and enhanced mechanical properties, the layer-by-layer technique was used for coating the surfaces of drug-loaded nanofibers by sequentially incorporating poly (sodium 4-styrene sulfonate) as a polyanion and poly (diallyldimethylammonium chloride) (PDADMAC) as a polycation. Various analyses, including scanning electron microscopy, Fourier transform infrared spectroscopy, drug release assessment., and mechanical tests were employed to assess the characteristics of the prepared wound dressings. Based on the results, coating with polyelectrolytes enhanced the Young's modulus and tensile strength of the electrospun mat from 1.34 MPa and 4.21 MPa to 1.88 MPa and 8.83 MPa, respectively. The coating also improved the controlled release of curcumin and antioxidant activity, while the outer layer, PDADMAC, exhibited antibacterial properties. The cell viability tests proved the appropriate biocompatibility of the prepared wound dressings. Moreover, our findings show that incorporation of the coating layers enhances cell migration and provides a favorable surface for cell attachment. According to the findings of this study, the fabricated nanofibrous wound dressing can be considered a promising and effective therapeutic intervention for wound management, facilitating the healing process.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

Microplastics in maternal amniotic fluid and their associations with gestational age.

Microplastics (MPs) pollution is a growing global concern due to its potential threat to human health, particularly concerning fetal health. Nevertheless, few studies have examined the sources of fetal MPs exposure and its impact on fetal development. In this study, MPs levels in maternal amniotic fluid (AF) and their associations with measures of fetal growth were investigated. Specifically, 40 human AF samples were collected to determine the presence and characteristics of MPs using laser direct infrared (LD-IR) spectroscopy. MPs were found in 32 out of 40 AF samples, with an average abundance of 2.01 ± 4.19 particles/g. Polyethylene (PE, 38.80 %) and chlorinated polyethylene (CPE, 26.98 %) were the most prevalent polymers. The majority of MPs (87.56 %) were 20-100 µm in size, and fragments (71.23 %) evidently prevailed in morphology. Additionally, a questionnaire was designed to explore the associations between MPs levels in the AF and maternal dietary habits, aiming at unveiling the potential sources of MPs in AF. The MPs levels in the AF were positively associated with the frequency of seafood consumption (r = 0.781, P < 0.001) and bottled water intake (r = 0.386, P = 0.014). Moreover, the associations between MPs levels in maternal AF and measures of fetal growth were evaluated. The abundance of total MPs in maternal AF were significantly negatively associated with gestational age (ß = -0.44, 95 % CI, -0.83, -0.05). This study confirms the presence of MPs in human AF and provides compelling evidence linking them to gestational age, while highlighting the potential risks associated with dietary habits. These findings underscore the need for further investigation into the mechanisms of MPs transmission from mother to fetus and the potential health implications during fetal development, offering valuable insights for future policies aimed at safeguarding maternal and fetal health.

Accumulation of microplastics in predatory birds near a densely populated urban area.

The pollution due to plastic and other anthropogenic particles has steadily increased over the last few decades, presenting a significant threat to the environment and organisms, including avian species. This research aimed to investigate the occurrence of anthropogenic pollutants in the digestive and respiratory systems of four birds of prey: Common Buzzard (Buteo buteo), Black Kite (Milvus migrans), Eurasian Sparrowhawk (Accipiter nisus), and Northern Goshawk (Accipiter gentilis). The results revealed widespread contamination in all species with microplastics (MPs) and cellulosic anthropogenic fibers (AFs), with an average of 7.9 MPs and 9.2 AFs per specimen. Every digestive system contained at least one MP, while 65 % of specimens exhibited MPs in their respiratory systems. This is the work reporting a high incidence of MPs in the respiratory system of birds, clearly indicating inhalation as a pathway for exposure to plastic pollution. The content of MPs and AFs varied significantly when comparing specimens collected from central Madrid with those recovered from other parts of the region, including rural environments, suburban areas, or less populated cities. This result aligns with the assumption that anthropogenic particles disperse from urban centers to surrounding areas. Additionally, the dominant particle shape consisted of small-sized fibers (> 98 %), primarily composed of polyester, polyethylene, acrylic materials, and cellulose fibers exhibiting indicators of industrial treatment. These findings emphasize the necessity for further research on the impact of plastic and other anthropogenic material contamination in avian species, calling for effective strategies to mitigate plastic pollution.

Predictability of implant sizes during cruciate-retaining total knee arthroplasty using an image-free hand-held robotic system.

The use of appropriately sized implants is critical for achieving optimal gap balance following total knee arthroplasty (TKA). Inappropriately sized implants could result in several complications. Robot-assisted TKA (RA-TKA) using CT-based pre-operative planning predicts implant sizes with high accuracy. There is scant literature describing the accuracy of image-free RA-TKA in predicting implant sizes. The purpose of this study was to assess the accuracy of an image-free robotic system in predicting implant sizes during RA-TKA. Patients who underwent cruciate-retaining RA-TKA for primary osteoarthritis, using an image-free hand-held robotic system were studied. The predicted and implanted sizes of the femoral component, tibial component and polyethylene insert, for 165 patients, were recorded. Agreement between robot-predicted and implanted component sizes was assessed in percentages, while reliability was assessed using Cohen's weighted kappa coefficient. The accuracy of the robotic system was 63% (weighted-kappa = 0.623, P < 0.001), 94% (weighted-kappa = 0.911, P < 0.001) and 99.4% (weighted-kappa = 0.995, P < 0.001), in predicting exact, ± 1 and ± 2 sizes of the femoral component, respectively. For the tibial component, an accuracy of 15.8% (weighted-kappa = 0.207, P < 0.001), 55.8% (weighted-kappa = 0.378, P < 0.001) and 76.4% (weighted-kappa = 0.568, P < 0.001) was noted, for predicting exact, ± 1 and ± 2 sizes respectively. An accuracy of 88.5%, 98.2% and 100%, was noted for predicting exact, ± 1 and ± 2 sizes of the polyethylene insert respectively. Errors in predicting accurate implant sizes could be multi-factorial. Though the accuracy of image-free RA-TKA with respect to alignment and component positioning is established, the surgeon's expertise should be relied upon while deciding appropriate implant sizes.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

The quantification of the airborne plastic particles of 0.43-11 µm: Procedure development and application to atmospheric environment.

The environmental degradation of microplastics results in ultrafine particles that may incur severe biological concerns. Despite this, the atmospheric existence of plastics of less than a few microns has barely been investigated due to the particle size limit of conventional analytical methods. This study develops a procedure to quantify and characterize plastic particles (including nanoplastics; less than 1 µm) in the air through fractional sampling, a simple pretreatment method, and pyrolysis-gas chromatography-mass spectrometry (pyr-GC/MS). We targeted 11 major polymers, namely, polyethylene, polypropylene, polystyrene, acrylonitrile-butadiene-styrene resin, styrene-butadiene rubber, polymethylmethacrylate, polycarbonate, polyvinyl chloride, polyethylene terephthalate (PET), polyamide 6, and polyamide 66 (PA66). The average spike and recovery rate of each polymer in the aerosol collected on the roof of a four-story building near a major road in Kyoto, Japan, amounted to 78-130%, with a coefficient of variation of less than 15%. By coupling pyr-GC/MS analysis with fractional sampling of particles within the size range of >11 µm, 11-7.0 µm, 7.0-4.7 µm, 4.7-3.3 µm, 3.3-2.1 µm, 2.1-1.1 µm, 1.1-0.65 µm, 0.65-0.43 µm, it was possible to quantify airborne nano- and microplastics by particle size. Polyethylene, polystyrene, PET, and PA66 were detected in the air, and the total mass concentration of tiny plastic particles (0.43-11 µm) amounted to 1.20 µg/m3. This translates into total particle numbers of 3.05 × 106 particles/m3 (assuming spheres), revealing a substantial number of particles under 1 µm. These results will contribute to future studies to understand the atmospheric behaviors of ultrafine plastic particles and their flow-on effects on the respiratory system.