3D-printed versatile biliary stents with nanoengineered surface for anti-hyperplasia and antibiofilm formation.

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

Background: The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. Methods: AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Results: Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. Conclusion: This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Lyoprotectant Constituents Suited for Lyophilization and Reconstitution of Stem-Cell-Derived Extracellular Vesicles.

Stem-cell-derived extracellular vesicles (EVs) are emerging as an alternative approach to stem cell therapy. Successful lyophilization of EVs could enable convenient storage and distribution of EV medicinal products at room temperature for long periods, thus considerably increasing the accessibility of EV therapeutics to patients. In this study, we aimed to identify an appropriate lyoprotectant composition for the lyophilization and reconstitution of stem-cell-derived EVs. MSC-derived EVs were lyophilized using different lyoprotectants, such as dimethyl sulfoxide, mannitol, trehalose, and sucrose, at varying concentrations. Our results revealed that a mixture of trehalose and sucrose at high concentrations could support the formation of amorphous ice by enriching the amorphous phase of the solution, which successfully inhibited the acceleration of buffer component crystallization during lyophilization. Lyophilized and reconstituted EVs were thoroughly evaluated for concentration and size, morphology, and protein and RNA content. The therapeutic effects of the reconstituted EVs were examined using a tube formation assay with human umbilical vein endothelial cells. After rehydration of the lyophilized EVs, most of their generic characteristics were well-maintained, and their therapeutic capacity recovered to levels similar to those of freshly collected EVs. The concentrations and morphologies of the lyophilized EVs were similar to the initial features of the fresh EV group until day 30 at room temperature, although their therapeutic capacity appeared to decrease after 7 days. Our study suggests an appropriate composition of lyoprotectants, particularly for EV lyophilization, which could encourage the applications of stem-cell-derived EV therapeutics in the health industry.

Assessing the impact of mRNA vaccination in chronic inflammatory murine model.

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

Gate Capacitance Coupling of Double-Gate Carbon Nanotube Network Transistors.

Carbon nanotube (CNT) network channels constructed using a high-purity CNT solution for use in CNT thin-film transistors have the advantages of the possibility of requiring a low-temperature process and needing no special equipment. However, there are empty spaces between individual CNTs, resulting in unexpected effects. In this study, double-gate (DG) CNT network transistors were fabricated and measured in four different configurations to observe the capacitive coupling effects between the top gate (TG) and bottom gate (BG) in the DG structure. As a result, the electrical characteristics measured with the BG with a thicker gate oxide while floating the TG were similar to those measured with the TG with a thinner gate oxide. A comparison of the measured transfer curves showed that TG and BG were strongly coupled through the empty spaces in the channels. In addition, we evaluated the capacitance coupling effect due to changes in the CNT density, which is closely related to the empty space of the network channel. Finally, we proposed a method to determine the effective gate capacitance by considering the empty spaces between CNTs, which enabled the accurate evaluation of mobility. The effects of these materials were demonstrated by fabricating transistors using Al2O3, HfO2, and ZrO2 as TG oxide materials. By focusing on considerations based on the properties of CNT materials, our study provides valuable insights into accurate electrical modeling and potential advancements in CNT-based devices.

Observing growth and interfacial dynamics of nanocrystalline ice in thin amorphous ice films.

Ice crystals at low temperatures exhibit structural polymorphs including hexagonal ice, cubic ice, or a hetero-crystalline mixture of the two phases. Despite the significant implications of structure-dependent roles of ice, mechanisms behind the growths of each polymorph have been difficult to access quantitatively. Using in-situ cryo-electron microscopy and computational ice-dynamics simulations, we directly observe crystalline ice growth in an amorphous ice film of nanoscale thickness, which exhibits three-dimensional ice nucleation and subsequent two-dimensional ice growth. We reveal that nanoscale ice crystals exhibit polymorph-dependent growth kinetics, while hetero-crystalline ice exhibits anisotropic growth, with accelerated growth occurring at the prismatic planes. Fast-growing facets are associated with low-density interfaces that possess higher surface energy, driving tetrahedral ordering of interfacial H2O molecules and accelerating ice growth. These findings, based on nanoscale observations, improve our understanding on early stages of ice formation and mechanistic roles of the ice interface.

A strategy for enhancing bioactivity and osseointegration with antibacterial effect by incorporating magnesium in polylactic acid based biodegradable orthopedic implant.

Biodegradable orthopedic implants are essential for restoring the physiological structure and function of bone tissue while ensuring complete degradation after recovery. Polylactic acid (PLA), a biodegradable polymer, is considered a promising material due to its considerable mechanical properties and biocompatibility. However, further improvements are necessary to enhance the mechanical strength and bioactivity of PLA for reliable load-bearing orthopedic applications. In this study, a multifunctional PLA-based composite was fabricated by incorporating tricalcium phosphate (TCP) microspheres and magnesium (Mg) particles homogenously at a volume fraction of 40 %. This approach aims to enhance mechanical strength, accelerate pore generation, and improve biological and antibacterial performance. Mg content was incorporated into the composite at varying values of 1, 3, and 5 vol% (referred to as PLA/TCP-1 Mg, PLA/TCP-3 Mg, and PLA/TCP-5 Mg, respectively). The compressive strength and stiffness were significantly enhanced in all composites, reaching 87.7, 85.9, and 84.1 MPa, and 2.7, 3.0, and 3.1 GPa, respectively. The degradation test indicated faster elimination of the reinforcers as the Mg content increased, resulting in accelerated pore generation to induce enhanced osseointegration. Because PLA/TCP-3 Mg and PLA/TCP-5 Mg exhibited cracks in the PLA matrix due to rapid corrosion of Mg forming corrosion byproducts, to optimize the Mg particle content, PLA/TCP-1 Mg was selected for further evaluation. As determined by in vitro biological and antibacterial testing, PLA/TCP-1 Mg showed enhanced bioactivity with pre-osteoblast cells and exhibited antibacterial properties by suppressing bacterial colonization. Overall, the multifunctional PLA/TCP-Mg composite showed improved mechanobiological performance, making it a promising material for biodegradable orthopedic implants.

Association of a Bioimpedance Profile with Optical Coherence Tomography Features in Diabetic Macular Edema.

We examined the association between bioimpedance profiles and optical coherence tomography (OCT) features in patients with diabetic macular edema (DME). This cross-sectional study included 100 eyes of 100 patients with type 2 diabetes mellitus. The systemic fluid status was assessed using extracellular water-to-total body water ratio (ECW/TBW) and phase angle (PhA), which was measured using bioimpedance equipment. ECW/TBW was higher in the DR (diabetic retinopathy) with DME group than in the no DR and DR without DME groups (p = 0.007 and p = 0.047, respectively); however, no significant difference was observed between the no DR and DR without DME groups. The PhA values were significantly lower in the DR with DME group (5.45 ± 0.84) than in the no DR (6.69 ± 0.69) and DR without DME groups (6.05 ± 1.15) (p < 0.001, p = 0.032, respectively). The presence of multiple HRF (hyper-reflective foci) was associated with a significantly higher ECW/TBW (p = 0.001). In the group with the most significant HRF, PhA was lower than in those with none or moderate amounts of HRF (p < 0.05). Bioimpedance fluid profiles of patients with OCT features of DME suggest a connection between the overall systemic state, including fluid status and DME development. Further research is required to fully understand and utilize this information for effective clinical assessment and treatment planning.

Wafer-scale striped network transistors based on purified semiconducting carbon nanotubes for commercialization.

Highly purified and solution-processed semiconducting carbon nanotubes (s-CNTs) have developed rapidly over the past several decades and are near-commercially available materials that can replace silicon due to its large-area substrate deposition and room-temperature processing compatibility. However, the more s-CNTs are purified, the better their electrical performance, but considerable effort and long centrifugation time are required, which can limit commercialization due to high manufacturing costs. In this work, we therefore fabricated 'striped' CNT network transistor across industry-standard 8 inch wafers. The stripe-structured channel is effective in lowering the manufacturing cost because it can maintain good device performance without requiring high-purity s-CNTs. We evaluated the electrical performances and their uniformity by demonstrating striped CNT network transistors fabricating from various s-CNT solutions (e.g. 99%, 95%, and 90%) in 8 inch wafers. From our results, we concluded that by optimizing the CNT network configurations, CNTs can be sufficiently utilized for commercialization technology even at low semiconducting purity. Our approach can serve as a critical foundation for future low-cost commercial CNT electronics.

Antibacterial PLA/Mg composite with enhanced mechanical and biological performance for biodegradable orthopedic implants.

Biodegradability, bone-healing rate, and prevention of bacterial infection are critical factors for orthopedic implants. Polylactic acid (PLA) is a good candidate biodegradable material; however, it has insufficient mechanical strength and bioactivity for orthopedic implants. Magnesium (Mg), has good bioactivity, biodegradability, and sufficient mechanical properties, similar to that of bone. Moreover, Mg has an inherent antibacterial property via a photothermal effect, which generates localized heat, thus preventing bacterial infection. Therefore, Mg is a good candidate material for PLA composites, to improve their mechanical and biological performance and add an antibacterial property. Herein, we fabricated an antibacterial PLA/Mg composite for enhanced mechanical and biological performance with an antibacterial property for application as biodegradable orthopedic implants. The composite was fabricated with 15 and 30 vol% of Mg homogeneously dispersed in PLA without the generation of a defect using a high-shear mixer. The composites exhibited an enhanced compressive strength of 107.3 and 93.2 MPa, and stiffness of 2.3 and 2.5 GPa, respectively, compared with those of pure PLA which were 68.8 MPa and 1.6 GPa, respectively. Moreover, the PLA/Mg composite at 15 vol% Mg exhibited significant improvement of biological performance in terms of enhanced initial cell attachment and cell proliferation, whereas the composite at 30 vol% Mg showed deteriorated cell proliferation and differentiation because of the rapid degradation of the Mg particles. In turn, the PLA/Mg composites exerted an antibacterial effect based on the inherent antibacterial property of Mg as well as the photothermal effect induced by near-infrared (NIR) treatment, which can minimize infection after implantation surgery. Therefore, antibacterial PLA/Mg composites with enhanced mechanical and biological performance may be a candidate material with great potential for biodegradable orthopedic implants.

Continuous production of lipid nanoparticles by multiple-splitting in microfluidic devices with chaotic microfibrous channels.

Polydimethylsiloxane (PDMS) microfluidic devices with chaotic microfibrous channels were fabricated for the continuous production of lipid nanoparticles (LNPs). Electrospun poly(ε-caprolactone) (PCL) microfibrous matrices with different diameters (3.6 ± 0.3, 6.3 ± 0.4, and 12.2 ± 0.8 µm) were used as a template to develop microfibrous channels. The lipid solution (in ethanol) and water phase were introduced into the microfluidic device as the discontinuous and continuous phases, respectively. The smaller diameter of microfibrous channels and the higher flow rate of the continuous phase resulted in the smaller LNPs with a narrower size distribution. The multiple-splitting of the discontinuous phase and the microscale contact between the two phases in the microfibrous channels were the key features of the LNP production in our approach. The LNPs containing doxorubicin with different average sizes (89.7 ± 35.1 and 190.4 ± 66.4 nm) were prepared using the microfluidic devices for the potential application in tumor therapy. In vitro study revealed higher cellular uptake efficiency and cytotoxicity of the smaller LNPs, especially in the HepG2 cells. The microfluidic devices with microfibrous channels can be widely used as a continuous and high-throughput platform for the production of LNPs containing various active agents.

Sub-10 fJ/bit radiation-hard nanoelectromechanical non-volatile memory.

With the exponential growth of the semiconductor industry, radiation-hardness has become an indispensable property of memory devices. However, implementation of radiation-hardened semiconductor memory devices inevitably requires various radiation-hardening technologies from the layout level to the system level, and such technologies incur a significant energy overhead. Thus, there is a growing demand for emerging memory devices that are energy-efficient and intrinsically radiation-hard. Here, we report a nanoelectromechanical non-volatile memory (NEM-NVM) with an ultra-low energy consumption and radiation-hardness. To achieve an ultra-low operating energy of less than 10 [Formula: see text], we introduce an out-of-plane electrode configuration and electrothermal erase operation. These approaches enable the NEM-NVM to be programmed with an ultra-low energy of 2.83 [Formula: see text]. Furthermore, due to its mechanically operating mechanisms and radiation-robust structural material, the NEM-NVM retains its superb characteristics without radiation-induced degradation such as increased leakage current, threshold voltage shift, and unintended bit-flip even after 1 Mrad irradiation.

Two-dimensional demixing within multilayered nanoemulsion films.

Benefiting from the demixing of substances in the two-phase region, a smart polymer laminate film system that exhibits direction-controlled phase separation behavior was developed in this study. Here, nanoemulsion films (NEFs) in which liquid nanodrops were uniformly confined in a polymer laminate film through the layer-by-layer deposition of oppositely charged emulsion nanodrops and polyelectrolytes were fabricated. Upon reaching a critical temperature, the NEFs exhibited a micropore-guided demixing phenomenon. A simulation study based on coarse-grained molecular dynamics revealed that the perpendicular diffusion of oil droplets through the micropores generated in the polyelectrolyte layer is crucial for determining the coarsening kinetics and phase separation level, which is consistent with the experimental results. Considering the substantial advantages of this unique and tunable two-dimensional demixing behavior, the viability of using the as-proposed NEF system for providing an efficient route for the development of smart drug delivery patches was demonstrated.

Swept-Source OCT Angiography Features in Patients after Macular Hole Surgery.

This study aimed to compare findings of optical coherence tomography (OCT) angiography (OCTA) between eyes with nearly recovered and partially recovered outer retina after full-thickness macular hole (FTMH) surgery and to identify OCTA findings associated with visual acuity. We retrospectively reviewed 30 patients who underwent surgery for idiopathic FTMH. Swept-source OCT (SS-OCT) and OCTA were performed preoperatively and at three and six months postoperatively. Subgroups were divided according to the integrity of the external limiting membranes and ellipsoid zones postoperatively. Correlations of best-corrected visual acuity six months postoperatively with SS-OCT and OCTA measurements were analyzed. There was no difference in preoperative retinal or choroidal vascular index on OCTA between the nearly and partially recovered groups. Six months postoperatively, the choriocapillaris flow-void area was significantly higher in the partially recovered group than in the fellow eye. The nearly recovered group showed better choroidal vascular flow, and vision at six months postoperatively correlated with the ratio of the operated eye's choriocapillaris flow-void area to the fellow eye. Sufficient choriocapillaris flow on OCTA is associated with better outer retinal recovery and visual outcomes after macular hole surgery.

Synthesis of soluble melanin nanoparticles under acidic conditions using Burkholderia cepacia tyrosinase and their characterization.

Melanin nanoparticles (MNPs) used for biomedical applications are often synthesized via the chemical auto-oxidation of catecholic monomers such as dopamine and 3,4-dihydroxyphenylalanine (DOPA) under alkaline conditions. However, the synthetic method for the chemical synthesis of MNP (cMNP) is relatively straightforward and more robust to control their homogenous particle size and morphology than the corresponding enzymatic synthetic methods. In this study, we demonstrated that the simple enzymatic synthesis of MNPs (eMNPs) with homogenous and soluble (<20 nm diameter) properties is possible using dopamine and Burkholderia cepacia tyrosinase (BcTy) under acidic conditions (i.e., pH 3.0). BcTy was highly reactive under pH 5.0, where the natural and chemical oxidation of catechol is complex, and thus melanin was synthesized via the hydroxylation of phenolic substrates. The detailed chemical analysis and characterization of the physical properties of the eMNPs confirmed the higher preservation of the catechol and primary amine moieties in the monomer substrate such as dopamine under acidic conditions. The eMNPs showed enhanced antioxidant activity and conferred stickiness to the formed hydrogel compared to the chemical auto-oxidation method owing to the large number of hydroxyl groups remaining such as catechol and quinone moieties. Because of these advantages and characteristics, the synthesis of MNPs using BcTy under acidic conditions can open a new path for their biomedical applications.

Fabrication of Micro-Patterned Chip with Controlled Thickness for High-Throughput Cryogenic Electron Microscopy.

A major limitation for the efficient and high-throughput structure analysis of biomolecules using cryogenic electron microscopy (cryo-EM) is the difficulty of preparing cryo-EM samples with controlled ice thickness at the nanoscale. The silicon (Si)-based chip, which has a regular array of micro-holes with graphene oxide (GO) window patterned on a thickness-controlled silicon nitride (SixNy) film, has been developed by applying microelectromechanical system (MEMS) techniques. UV photolithography, chemical vapor deposition, wet and dry etching of the thin film, and drop-casting of 2D nanosheet materials were used for mass-production of the micro-patterned chips with GO windows. The depth of the micro-holes is regulated to control the ice thickness on-demand, depending on the size of the specimen for cryo-EM analysis. The favorable affinity of GO toward biomolecules concentrates the biomolecules of interest within the micro-hole during cryo-EM sample preparation. The micro-patterned chip with GO windows enables high-throughput cryo-EM imaging of various biological molecules, as well as inorganic nanomaterials.

Analysis of MicroRNA Expression in Tears of Patients with Herpes Epithelial Keratitis: A Preliminary Study.

Purpose: Herpes epithelial keratitis (HEK) is the most common form of herpes simplex virus (HSV) eye involvement, and understanding the molecular mechanisms underlying HEK is important. We investigated the expression of microRNAs (miRNAs) in the tears of patients with HEK. Methods: Tear samples from eight patients with HEK and seven age-matched controls were evaluated. Clinical ophthalmologic evaluation was performed, and an anterior segment photograph was obtained after fluorescence staining. Dendritic or geographic ulcer areas were measured using ImageJ software. The expression of 43 different miRNAs in tears was measured using real-time polymerase chain reaction and compared between patients with HEK and controls. Differences in miRNA expression between the dendritic and geographic ulcer groups and correlations involving miRNA expression and ulcer area were evaluated. Results: Of the 43 miRNAs, 23 were upregulated in patients with HEK compared to normal controls. MiR-15b-5p, miR-16-5p, miR-20b-5p, miR-21-5p, miR-23b-3p, miR-25-3p, miR-29a-3p, miR-30a-3p, miR-30d-5p, miR-92a-3p, miR-124-3p, miR-127-3p, miR-132-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-146b-5p, miR-155-5p, miR-182-5p, miR-183-5p, miR-221-3p, miR-223-3p, and miR-338-5p were significantly upregulated in patients with HEK. MiR-29a-3p exhibited significant differences between the dendritic and geographic ulcer groups. All 23 miRNAs with significant differences between patients with HEK and the control group were not significantly correlated with ulcer area. Conclusions: Twenty-three miRNAs were significantly upregulated in the tears of patients with HEK, and the expression of miRNAs may play important roles in herpes infection in relation to host immunity.

Cost-effective method for fabricating carbon nanotube network transistors by reusing a 99% semiconducting carbon nanotube solution.

Carbon nanotubes (CNTs) are one-dimensional materials that have been proposed to replace silicon semiconductors and have been actively studied due to their high carrier mobility, high current density, and high mechanical flexibility. Specifically, highly purified, pre-separated, and solution-processed semiconducting CNTs are suitable for mass production. These CNTs have advantages, such as room-temperature processing compatibility, while enabling a fast and straightforward manufacturing process. In this paper, CNT network transistors were fabricated on a total of five 8 inch wafers by reusing a highly purified and pre-separated 99% semiconductor-enriched CNT solution. The results confirmed that the density of semiconducting CNTs deposited on the five selected wafers was notably uniform, even though the CNT solution was reused up to four times after the initial CNT deposition. Moreover, there was no significant degradation in the key CNT network transistor metrics. Therefore, we believe that our findings regarding this CNT reuse method may provide additional guidance in the field of wafer-scale CNT electronics and may contribute strongly to the development of practical device applications at an ultralow cost.