Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning.

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

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.

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.

Production of Bioactive Substances to Alleviates Hangover and Ethanol-Induced Liver Damage through Fermentation of Oenanthe javanica Using Lactiplantibacillus plantarum.

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.

Structuring Pickering Emulsion Interfaces with Bilayered Coacervates of Cellulose Nanofibers and Hectorite Nanoplatelets.

In this study, we present a water-in-silicone oil (W/S) Pickering emulsion system stabilized via in situ interfacial coacervation of attractive hectorite nanoplatelets (AHNPs) and bacterial cellulose nanofibrils (BCNFs). A bilayered coacervate is generated at the W/S interface by employing the controlled electrostatic interaction between the positively charged AHNPs and the negatively charged BCNFs. The W/S interface with the bilayered coacervate shows a significant increase in the interfacial modulus by 2 orders of magnitude than that with the AHNPs only. In addition, we observe that water droplets are interconnected by the BCNF bridging across the continuous phase of silicon, which is attributed to the diffusive transport phenomenon. This droplet interconnection results in the effective prevention of drop coalescence, which is confirmed via emulsion sedimentation kinetics. These results indicate that our bilayered coacervation technology has the potential of developing a promising Pickering emulsion platform that can be used in the pharmaceutical and cosmetic industries.

Wafer-scale carbon nanotube network transistors.

Highly purified, preseparated semiconducting carbon nanotubes (CNTs) hold great potential for high-performance CNT network transistors due to their high electrical conductivity, high mechanical strength, and room-temperature processing compatibility. In this paper, we report our recent progress on CNT network transistors integrated on an 8-inch wafer. We observe that the key device performance parameters of CNT network transistors at various locations on an 8-inch wafer are highly uniform and that the device yield is impressive. Therefore, this work validates a promising path toward mass production and will make a significant contribution to the future field of wafer-scale CNT electronics.

Directly drawn top-gate semiconducting carbon nanotube thin-film transistors and complementary inverters.

As the emerging demand for electronic devices that are simple, cost effective and capable of rapid fabrication has increased, novel fabrication techniques for designing and manufacturing such devices have attracted remarkable research interest. One method for prototyping these electronic devices is to draw them using a handwriting tool that is commonly available. In this work, we demonstrate a transistor and complementary logic inverter that are directly drawn using a brush and that are based on solution-based materials such as semiconducting carbon nanotubes (CNTs), silver ink and paste, and cross-linked poly(4-vinylphenol) (cPVP). The directly drawn CNT thin-film transistor (TFT) has p-type behavior due to the adsorption of oxygen and moisture, a high current on/off ratio (approximately 103), and a low operating voltage. By employing a solution-based chemical doping treatment with an amine-rich polymer, polyethyleneimine (PEI), that has strong electron-donating ability, the drawn p-type CNT-TFT is successfully converted to an n-type CNT-TFT. Therefore, we fabricate a drawn complementary logic inverter consisting of the p-type CNT-TFT and PEI-treated n-type CNT-TFT and evaluate its electrical performance.

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

BACKGROUND: To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. METHODS: This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. RESULTS: After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). CONCLUSIONS: Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

Vertically Integrated Nanowire-Based Unified Memory.

A vertically integrated nanowire-based device for multifunctional unified memory that combine dynamic random access memory (DRAM) and flash memory in a single transistor is demonstrated for the first time. The device utilizes a gate-all-around (GAA) structure that completely surrounds the nanowire; the structure is built on a bulk silicon wafer. A vertically integrated unified memory (VIUM) device composed of five-story channels was fabricated via the one-route all-dry etching process (ORADEP) with reliable reproducibility, stiction-free stability, and high uniformity. In each DRAM and flash memory operation, the five-story VIUM showed a remarkably enhanced sensing current drivability compared with one-story unified memory (UM) characteristics. In addition to each independent memory mode, the switching endurance of the VIUM was evaluated in the unified mode, which alternatively activates two memory modes, resulting in an even higher sensing memory window than that of the UM. In addition to our previous work on a logic transistor joining high performance with good scalability, this work describes a novel memory hierarchy design with high functionality for system-on-chip (SoC) architectures, demonstrating the practicality and versatility of the vertically integrated nanowire configuration for use in various applications.

A Vertically Integrated Junctionless Nanowire Transistor.

A vertically integrated junctionless field-effect transistor (VJ-FET), which is composed of vertically stacked multiple silicon nanowires (SiNWs) with a gate-all-around (GAA) structure, is demonstrated on a bulk silicon wafer for the first time. The proposed VJ-FET mitigates the issues of variability and fabrication complexity that are encountered in the vertically integrated multi-NW FET (VM-FET) based on an identical structure in which the VM-FET, as recently reported, harnesses a source and drain (S/D) junction for its operation and is thus based on the inversion mode. Variability is alleviated by bulk conduction in a junctionless FET (JL-FET), where current flows through the core of the SiNW, whereas it is not mitigated by surface conduction in an inversion mode FET (IM-FET), where current flows via the surface of the SiNW. The fabrication complexity is reduced by the inherent JL structure of the JL-FET because S/D formation is not required. In contrast, it is very difficult to dope the S/D when it is positioned at each floor of a tall SiNW with greater uniformity and with less damage to the crystalline structure of the SiNW in a VM-FET. Moreover, when the proposed VJ-FET is used as nonvolatile flash memory, the endurance and retention characteristics are improved due to the above-mentioned bulk conduction.

Clinical outcomes for endovascular repair of abdominal aortic aneurysm with the Seal stent graft.

OBJECTIVE: Since 2007, the availability of the Seal (S & G Biotech Inc, Seong-nam, Gyeonggi-do, Korea) stent graft for endovascular aneurysm repair (EVAR) has improved short-term outcomes in Korea. However, midterm outcome data are lacking. This retrospective study evaluated the midterm outcomes of 126 patients who underwent EVAR using the Seal stent graft between 2007 and 2010. METHODS: Data regarding use of the Seal stent graft for EVAR were collected from 16 Korean centers, and were analyzed retrospectively using Kaplan-Meier and Cox univariate and multivariate analyses. RESULTS: The mean patient age was 71 ± 8 years (median, 70; range, 49-87 years). Patients who were treated using a bifurcated graft (113; 90%) were generally symptomatic (56; 44%, which included 13 ruptured abdominal aortic aneurysms [10%]) and male (105; 83%). The primary technical success rate was 99%. Four patients (3%) died within 30 days, 5 patients (4%) died after 30 days, and 12 patients (9%) were lost to follow-up. The survival rates were 97% ± 2% (1 month), 97% ± 2% (3 months), 96% ± 2% (6 months), 96% ± 2% (1 year), 94% ± 3% (3 years), and 81% ± 10% (5 years). During a mean follow-up of 55 ± 22 months (median, 40; range, 0.03-91.2 months), 18 reinterventions were performed for 16 patients (13%). The freedom from reintervention rates were 96% ± 2% (1 month), 96% ± 2% (3 months), 94% ± 2% (6 months), 89% ± 3% (1 year), 84% ± 4% (3 years), and 57% ± 17% (5 years). The mean aneurysm diameter significantly decreased from 69.6 to 46.6 mm during the follow-up (P < .0001). A proximal neck of less than 15 mm, different simultaneous endoleaks, and insufficient bilateral coverage of the iliac aneurysm were associated with significantly higher rates of increased or unchanged aneurysm diameters (all P < .0001). Significantly higher rates of clinical failure were observed in patients who were less than 70 years old (P = .04), had a neck length of less than 15 mm (P = .02), and had a neck diameter of greater than 28 mm (P = .02). CONCLUSIONS: Most Seal stent grafts were implanted successfully (even in cases with a physical status of grade IV or higher or a ruptured abdominal aortic aneurysm), had an appropriate reintervention rate, and were stable during the midterm follow-up. However, there was a high rate of type I endoleak, which may be related to the early device model that we used. Therefore, long-term radiologic follow-up is recommended for the early detection of stent graft migration or endoleaks.

Hydroxyapatite (HA)/poly-L-lactic acid (PLLA) dual coating on magnesium alloy under deformation for biomedical applications.

The introduction of a protective coating layer to highly corrosive magnesium (Mg) has been proposed as one of the common approaches for improved corrosion resistance of Mg-based implants as load-bearing biomedical applications. However, only few studies have focused on the mechanical stability of the coated Mg under practical conditions where significant deformation of the load-bearing implants is induced during the surgical operation or under physiological environments. Therefore, in this study, we developed a dual coating system composed of an interlayer hydroxyapatite (HA) and a top layer poly-L-lactic acid (PLLA) to improve the coating stability under deformation of Mg alloy (WE43) substrate. The HA interlayer was directly formed on the Mg alloy surface, followed by dip-coating of PLLA. As the interlayer, HA improved the adhesion of PLLA by modulating nano- and microscale roughness, in addition to its inherently good bonding strength to Mg. The flexible and deformable top coating PLLA layer mitigated crack propagation in the HA layer under deformation. Thus, the dual coating layer provided good protection to the underlying WE43 from corrosion regardless of deformation. The enhanced corrosion behavior of dual-coated WE43 exhibited better mechanical and biological performance compared to the non-coated or single-coated WE43. Therefore, this dual coating layer on Mg is expected to accelerate Mg-based applications in biomedical devices.

Vertically Integrated Multiple Nanowire Field Effect Transistor.

A vertically integrated multiple channel-based field-effect transistor (FET) with the highest number of nanowires reported ever is demonstrated on a bulk silicon substrate without use of wet etching. The driving current is increased by 5-fold due to the inherent vertically stacked five-level nanowires, thus showing good feasibility of three-dimensional integration-based high performance transistor. The developed fabrication process, which is simple and reproducible, is used to create multiple stiction-free and uniformly sized nanowires with the aid of the one-route all-dry etching process (ORADEP). Furthermore, the proposed FET is revamped to create nonvolatile memory with the adoption of a charge trapping layer for enhanced practicality. Thus, this research suggests an ultimate design for the end-of-the-roadmap devices to overcome the limits of scaling.

Relationship between divided-shaped kidney and collecting system duplication.

PURPOSE: We aimed to assess the incidence of divided-shaped kidney and the relationship between divided-shaped kidney and collecting system duplication. SUBJECTS AND METHODS: Between May 1 and June 30, 2012, 857 patients (men:women, 493:364; mean age 39.6 years; age range 2-98 years) with 1699 kidneys underwent enhanced computed tomography of the abdomen and pelvis at our institution. Sixty kidneys were excluded (tumor, 3; percutaneous nephrostomy, 9; polycystic kidney disease, 4; renal injury, 1; infarct, 1; hydronephrosis, 18; parapelvic cyst, 17; artifact, 5; horseshoe kidney, 2). Finally, 845 patients and 1639 kidneys were included. The number of cases of prominent column of Bertin (divided by grade of prominence as either divided-shaped kidney or hypertrophy) and collecting system duplication (bifid, partial, and complete) were evaluated. Fisher exact test was used to determine the relationship between divided-shaped kidney and collecting system duplication, and between hypertrophy and collecting system duplication. RESULTS: Of 1639 kidneys, 66 (4%) were divided-shaped kidneys, and 88 (5%) had collecting system duplication (bifid, 69; partial, 19; complete, 0); among the 66 divided-shaped kidneys, 28 (42%) had collecting system duplication. Among the 429 cases of hypertrophy and 1144 normal kidneys, 51 (11.9%) and 9 (0.8%) had collecting system duplication, respectively. CONCLUSIONS: The incidence of divided-shaped kidney was 4%, and there was a significant association between divided-shaped kidney and collecting system duplication.

Clinical measurement of the angle of ocular movements in the nine cardinal positions of gaze.

PURPOSE: To measure the maximum angle of ocular versions using photographs of the 9 cardinal positions and a modified limbus test. DESIGN: An evaluation of diagnostic technology; a prospective observational study. PARTICIPANTS: We enrolled 104 healthy subjects, 20 to 40 years of age. METHODS: Photographs were obtained in the 9 cardinal positions of gaze and the images were processed using Photoshop. The images were analyzed using the Image J program to measure the angle of version. The maximum angle of the 9 cardinal positions was quantified using a modified limbus test. MAIN OUTCOME MEASURES: We measured the maximum angle of ocular versions in the 9 cardinal positions of gaze. We also compared the results for males and females. RESULTS: The mean angles of maximum version were adduction 47.4°, abduction 46.4°, elevation 31.8°, depression 47.8°, elevation in adduction 39.7°, elevation in abduction 40.7°, depression in adduction 52.7°, and depression in abduction 49.2°. The mean angle of maximum elevation was significantly smaller than that of depression (P <0.001). There were no correlations between the angle of maximum version and age, spherical equivalents, or axial length. The angle of maximum version for males was significantly greater than that for females, except for inferior gaze. CONCLUSIONS: A modified limbus test using photographs of the 9 cardinal positions is an objective and reproducible tool for quantifying ocular movement. Considering its simplicity, ease of use, and low cost, it has clear applications in clinical practice.

Epithelial-mesenchymal transition-related protein expression in biliary epithelial cells associated with hepatolithiasis.

BACKGROUND AND AIM: Epithelial-mesenchymal transition (EMT) of biliary epithelial cells (BECs) plays major roles in many cholangiopathies. This study evaluated whether EMT of BECs has a role in hepatolithiasis-induced biliary fibrosis and types of BECs that are involved. METHODS: The expression of EMT-related proteins and epidermal growth factor receptor was evaluated by immunohistochemistry of liver tissues from 102 patients with hepatolithiasis, 32 patients with post-hepatitis cirrhosis, and 48 normal livers. Antibodies against E-cadherin, ß-catenin, and cytokeratin were used to identify epithelial cells and antibodies against vimentin, S100A4, podoplanin, and α-smooth muscle actin (α-SMA) were used to identify mesenchymal cells. The relationship between clinical and histological parameters and immunohistochemistry findings in BECs, and the surrounding stroma were evaluated. RESULTS: Loss of E-cadherin and acquisition of S100A4 and vimentin were observed in BECs. In all BECs, cytokeratin and ß-catenin expression were unchanged, while podoplanin and α-SMA were not expressed. Although hepatic fibrosis was more severe in post-hepatitis cirrhosis, EMT of BECs was more widespread in hepatolithiasis. In hepatolithiasis, EMT-related proteins were more highly expressed in small bile ducts than in medium or large bile ducts. Their expression was associated with the severity of biliary fibrosis and the expressions of epidermal growth factor receptor. Expression of α-SMA in fibroblasts from the portal space was closely linked to pathological changes in small bile ducts and EMT-related protein expressions in BECs. CONCLUSIONS: Proliferating cholangiocytes that form small bile ducts may contribute to cholangiopathies in hepatolithiasis through an EMT-like phenomenon or through interactions with stromal myofibroblasts.

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.

Repeatability of Scheimpflug-Placido camera in mild dry eye versus normal eyes according to the topographical position of the cornea.

We aimed to investigate the repeatability of various corneal measurements according to topographical location in the entire cornea measured by dual rotating Scheimpflug-Placido camera and to explore the differences in repeatability between patients with mild dry eye and those with normal eyes. In both the normal and dry eye groups, divided based on BUT or the height of the tear film, there were no statistically significant differences in the ratio of unacceptable variation (RUV) and ICC. The consistency of the examination of the anterior and posterior refractive values and corneal thickness according to the corneal location, measured three times repeatedly using the Galilei anterior segment camera, was high. There was no difference based on the height of the tear film or the tear film break-up time. However, caution is needed when interpreting the values of the anterior corneal refractive values, as there can be changes of more than 0.5D within 3 mm of the central area.

Bioinspired Nanotopography for Combinatory Osseointegration and Antibacterial Therapy.

The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant contributors to mortality rates. Orthopedic implants, while essential for trauma and orthopedic surgeries, are particularly susceptible to these infections, leading to severe complications and economic burdens. The traditional use of antibiotics in treating these infections poses further challenges including the risk of developing antibiotic-resistant bacteria. This study introduces a novel approach to combat this issue by developing nanostructured surfaces for orthopedic implants using target ion-induced plasma sputtering. Inspired by the natural design of dragonfly wings, these surfaces aim to prevent bacterial adhesion while promoting preosteoblast activity, offering a dual-function solution to the problems of bacterial infection and implant integration without relying on antibiotics. The in vitro results demonstrate the effectiveness of these bioinspired surfaces in eradicating bacteria and supporting cell proliferation and differentiation, presenting a promising alternative for the development of biomedical implants.

Incidence and risk factor analysis of neovascular glaucoma following vitrectomy in patients with proliferative diabetic retinopathy.

To investigate the incidence and risk factors for neovascular glaucoma (NVG) after vitrectomy in patients with proliferative diabetic retinopathy (PDR). Patients were categorized into two subgroups based on their treatment regimen: one group received vitrectomy only (Group 1), while the other received combined phacovitrectomy (Group 2). A comparative analysis was conducted to evaluate the distinguishing characteristics of the two groups. Kaplan-Meier survival analysis was used to determine the incidence of NVG following surgery. Furthermore, multivariate analysis using the Cox proportional hazards model was conducted to identify the risk factors associated with the development of NVG after surgery. A total of 484 eyes of 484 patients were included in the study. When comparing Group 1 with Group 2, a significant difference was observed in the occurrence of NVG. In Group 1, there were 10 cases of NVG (3.9%), whereas 29 cases of NVG occurred in Group 2 (12.71%). Male sex, high preoperative intraocular pressure (IOP), and combined phacovitrectomy were found to be associated with the occurrence of NVG following phacovitrectomy. Higher creatinine levels had a protective effect in preventing the development of NVG. Male sex, high preoperative IOP, and combined phacovitrectomy were associated with a high incidence of NVG. Explore strategies to prevent NVG is important when performing combined phacovitrectomy in patients with PDR.