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High-aspect-ratio patterns are required for next-generation three-dimensional (3D) semiconductor devices. However, it is challenging to eliminate voids and seams during gap-filling of these high-aspect-ratio patterns, such as deep trenches, especially for nanoscale high-aspect-ratio patterns. In this study, a SiO2plasma-enhanced atomic layer deposition process incorporated with ion collision using bias power to the substrate was used for bottom-up trench gap-filling. The effect of bias power frequency on SiO2trench gap-filling was then investigated. Results showed that changes in bias power frequency did not significantly change the process rate, such as SiO2growth per cycle. At relatively low bias power frequencies, high-energy ions formed an overhang at the entrance of the high-aspect-ratio trench pattern through sputter etching and redeposition, blocking the pattern entrance. However, at relatively high-frequency bias power, overhang formation due to sputtering did not occur. In the trench interior, due to a scattering effect of ions, deposition was thicker at the bottom of the trench than that at the top, achieving bottom-up gap-filling and void-free gap-filling.

Background: Dry powder inhalation (DPI) formulations have been widely studied for the treatment of respiratory diseases, including COVID-19, which have become common and dangerous worldwide. Dry powder inhalation formulations have become a popular approach for targeted drug delivery to the lungs. Inhalation offers advantages over other administration routes by providing direct treatment and action to alleviate and manage respiratory conditions. Area covered: This review covers the anatomical and physiological characteristics of the human respiratory tract and the considerations that need to be considered when formulating DPIs. It also provides an overview of current inhalation products and clinical trials in the treatment of respiratory diseases such as asthma, COPD, IPF, PAH, tuberculosis, and COVID-19. Additionally, various methods of particle preparation for DPI formulations are described, including conventional techniques such as milling and spray drying, and novel techniques such as SFD, SCF, TFF, HME, and PRINT. Expert opinion: DPIs are typically prepared by using conventional and novel particle preparation techniques, but these methods may require specialized equipment and have some limitations. Moreover, the number of approved inhalable excipients is limited, which hinders further development of DPI formulations. To address this, the development and approval of new inhalable excipients is needed, and the use of new technologies and excipients is expected to overcome the limitations of DPI formulations.

Abstract: This study presents a novel methodology for the fabrication of bioadhesives composed of poly(2-hydroxyethyl acrylate) (PHEA), which demonstrate superior mechanical properties. Hydrogels based on PHEA were effectively synthesized through a strategy that obviates the need for crosslinkers, utilizing in situ polymerization of high-concentration 2-hydroxyethyl acrylate (HEA) monomers under persistent agitation. Optimal operational conditions, such as polymerization duration and HEA monomer concentration, were screened through rheological evaluations. In addition, the introduction of glycerol to the PHEA hydrogels yielded improvements in water-retention capacity, thus resolving limitations frequently observed in conventional aqueous-based hydrogels. Tests assessing adhesive properties indicated that the PHEA hydrogels, synthesized without crosslinkers, exhibited exceptional adhesion capabilities that exceeded those of commercially available tissue sealants. This economically viable and readily scalable fabrication technique provides a compelling pathway for the creation of robust, biocompatible bioadhesives well-suited for biomedical utilization. Graphical abstract:

Memristive technology has been rapidly emerging as a potential alternative to traditional CMOS technology, which is facing fundamental limitations in its development. Since oxide-based resistive switches were demonstrated as memristors in 2008, memristive devices have garnered significant attention due to their biomimetic memory properties, which promise to significantly improve power consumption in computing applications. Here, we provide a comprehensive overview of recent advances in memristive technology, including memristive devices, theory, algorithms, architectures, and systems. In addition, we discuss research directions for various applications of memristive technology including hardware accelerators for artificial intelligence, in-sensor computing, and probabilistic computing. Finally, we provide a forward-looking perspective on the future of memristive technology, outlining the challenges and opportunities for further research and innovation in this field. By providing an up-to-date overview of the state-of-the-art in memristive technology, this review aims to inform and inspire further research in this field.

The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells. In this study, SD rats were divided into the normal chow diet group (NCD), high fat diet group (HFD), three treatment groups feeding high-fat diet with naringenin (100, 200, 400 mg/kg) for 12 weeks. Results indicated that naringenin treatment decreased total cholesterol (TC), triglyceride (TG) and the non-high-density lipoprotein cholesterol (non-HDL-C) levels in serum. Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats. In addition, naringenin (25−75 µg/mL) decrease TG and TC levels in 3T3 mature adipocytes. The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology. Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes.Meanwhile, naringenin increased the AMPK (AMP-activated protein kinase) activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes. And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C. Molecular docking results indicated that naringenin could bind to AMPK protein. These results indicated naringenin reduced lipid accumulation through AMPK pathway.

Plasma enhanced atomic layer deposition (PEALD) of silicon nitride (SiNx) using very high frequency (VHF, 162 MHz) plasma source was investigated at the process temperatures of 100, 200, and 300 °C. Two aminosilane precursors having different numbers of amino ligands, bis(tert-butylamino)silane (BTBAS) and di(sec-butylamino)silane (DSBAS), were used as Si precursors. A comparative study was also conducted to verify the effect of the number of amino ligands on the properties of SiNxfilm. At all process temperatures, DSBAS, having one amino ligand, performed better than BTBAS in various aspects. SiNxfilms deposited using DSBAS had lower surface roughness, higher film density, lower wet etch rate, improved electrical characteristics, and higher growth rate than those deposited using BTBAS. With the combination of a VHF plasma source and DSBAS with one amino ligand, the SiNxfilms grown at 300 °C exhibited low wet etch rates (≤2 nm/min) in a dilute HF solution (100:1 of deionized water:HF) as well as low C content below the XPS detection limit. Also, excellent step coverage close to 100% on high aspect ratio (30:1) trench structures was obtained by using VHF plasma, which could provide sufficient flux of plasma species inside the trenches in conjunction with DSBAS having fewer amino ligands than BTBAS.

Micro-LEDs (µLEDs) have been explored for augmented and virtual reality display applications that require extremely high pixels per inch and luminance1,2. However, conventional manufacturing processes based on the lateral assembly of red, green and blue (RGB) µLEDs have limitations in enhancing pixel density3–6. Recent demonstrations of vertical µLED displays have attempted to address this issue by stacking freestanding RGB LED membranes and fabricating top-down7–14, but minimization of the lateral dimensions of stacked µLEDs has been difficult. Here we report full-colour, vertically stacked µLEDs that achieve, to our knowledge, the highest array density (5,100 pixels per inch) and the smallest size (4 µm) reported to date. This is enabled by a two-dimensional materials-based layer transfer technique15–18that allows the growth of RGB LEDs of near-submicron thickness on two-dimensional material-coated substrates via remote or van der Waals epitaxy, mechanical release and stacking of LEDs, followed by top-down fabrication. The smallest-ever stack height of around 9 µm is the key enabler for record high µLED array density. We also demonstrate vertical integration of blue µLEDs with silicon membrane transistors for active matrix operation. These results establish routes to creating full-colour µLED displays for augmented and virtual reality, while also offering a generalizable platform for broader classes of three-dimensional integrated devices.

Owning to their unusual optical properties, such as electrical tunability and strong spatial confinement, two-dimensional surface polaritons (2DSPs) hold great promise for deep sub-wavelength manipulation of light in a reduced low-dimensional space. Control of 2DSPs is possible by using their interaction with a boundary between two media, similar to how light behaves in three-dimensional (3D) space. The understanding of the interaction in the 2D case is still in its early stages, unlike the 3D case, as in-depth investigations are only available in a few cases including the interaction of 2DSPs with structured 2D crystals. Here, we extend the scope of our understanding to the interaction of 2DSPs with metallic nano-plates on 2D crystals, focusing on the reflection of 2DSPs. Through our rigorous model, we reveal that, for strongly confined 2DSPs having much larger momentum than free space photons, the interaction results in almost total internal reflection of 2DSPs as the radiative coupling of the 2DSPs to free space is negligible. We also find that the reflection involves an anomalous phase shift dependent on the thickness of the nano-plate, due to the temporary storing of electromagnetic energy in the evanescent waves induced near the edge of the nano-plate. Our theory predicts that the phase shift saturates to an anomalous value, 0.885π, as the nano-plate becomes thicker. Our work provides a detailed understanding of how to manipulate the 2DSPs by using one of the simplest nanostructures, essential for the further development of nanostructure-integrated low-dimensional devices for polariton optics.

Purpose: Pirfenidone (PRF) is the first FDA-approved active pharmaceutical ingredient for the treatment of idiopathic pulmonary fibrosis (IPF). However, it has severe adverse effects such as photophobia and gastrointestinal disorder. Administration of PRF through the pulmonary route requires a relatively low effective dose and has few adverse effects. We evaluated the efficacy of inhalable PRF microparticles, which we manufactured via wet bead milling, to examine their bioavailability and efficacy when delivered through the pulmonary route as dry powder inhaler. Methods: Bead milled microparticles of PRF were prepared using high-energy dry or wet bead milling. Bioavailability of PRF was confirmed via in vivo pharmacokinetic (PK) experiments; in vivo pharmacodynamic experiments were performed using a bleomycin induced IPF rat model. Results: Wet bead milling was more efficient than dry bead milling owing to the high crystallinity and cohesiveness of PRF. Furthermore, in vivo PK experiments demonstrated that administering PRF via the pulmonary route was more than twice as effective as the oral route. Similarly, the therapeutic impact of PRF delivered via the pulmonary route was more optimized than that of PRF delivered via the oral route. Conclusion: These findings indicate that the bioavailability, distribution in the lungs, and therapeutic effect of PRF are superior when administered via the pulmonary route compared to the oral route.

Purpose: Systemic absorption is the process of drug movement from the site of drug administration to systemic circulation for therapeutic efficacy. Systemic absorption and distribution of therapeutics are affected by the route of administration and may further vary with different sites for the same route. Paclitaxel (PTX) remains one of the most powerful chemotherapeutic drugs to treat various tumors. Nevertheless, PTX has not been used to treat brain tumors because of its blood-brain barrier (BBB) impermeability and lack of drug accumulation in the brain. This study aimed to investigate systemic absorption and brain uptake of PTX following subcutaneous (SC) injection at different sites. Methods: A hydroxypropyl methylcellulose (HPMC) polymer was used to prepare the PTX-HPMC hydrogel. The PTX-HPMC hydrogel was characterized by sol-gel transition, drug release, and in situ hydrogel formation. Systemic absorption and distribution in the brain were investigated in mice after subcutaneous injection at three different sites (flank, head, and abdomen). The PTX concentrations in the plasma and brain homogenates were quantified using LC-MS/MS using the liquid-liquid extraction method. Results: The PTX-HPMC hydrogel showed sol-gel transition at 37 ℃ and bi-phase release with burst and sustained release. Systemic absorption in the plasma at all SC injection sites showed no significant differences. However, the distribution to the brain after SC injection at the head was 2.5 times higher than at the flank, suggesting an injection site-dependent distribution of PTX. Conclusion: Differences in blood and lymph flow among SC sites are expected to contribute to PTX distribution. SC injection into the head may be a promising route for drug delivery to brain.

Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.

Objective:The ion shift index (ISI), which considers extracellular fluid ions such as phosphate, calcium, and magnesium, represents the ion shift following ischemia; concentrations of these ions are maintained within narrow normal ranges by adenosine triphosphate-dependent homeostasis. The ISI is defined as follows: {potassium (mmol/L-1) + phosphate (mmol/L-1) + Mg (mmol/L-1)}/calcium (mmol/L-1). This study investigated the possibility of predicting the 30-day survival rate of patients who underwent traumatic damage control laparotomy by comparing ISI and other laboratory findings, as well as the initial Trauma and Injury Severity Score (TRISS) and shock indices. Methods:Among the 134 patients who underwent damage control surgery between November 2012 and December 2021, 115 patients were enrolled in this study. Data regarding injury mechanism, age, sex, laboratory findings, vital signs, Glasgow Coma Scale score, Injury Severity Score, Abbreviated Injury Scale score, blood component transfusion, type of surgery, postoperative laboratory outcomes, morbidity, mortality rates, fluids administered, and volume of transfusions were collected and analyzed. Results:In univariate analysis, the odds ratio of the initial ISI was 2.875 (95% confidence interval, 1.52–5.43; P= 0.04), which showed a higher correlation with mortality compared with other indices. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were derived from different multivariable logistic regression models. The initial ISI had high sensitivity and specificity in predicting patient mortality (AUC, 0.7378). In addition, in the model combining the initial ISI, crystalloids, and TRISS, the AUC showed a high value (AUC, 0.8227). Conclusion:The ISI evaluated using electrolytes immediately after admission in patients undergoing traumatic damage control surgery may be a predictor of patient mortality.

We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule’s structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.

In 2019 September, a sudden flare of the 6.7 GHz methanol maser was observed toward the high-mass young stellar object (HMYSO) G24.33+0.14. This may represent the fourth detection of a transient mass accretion event in an HMYSO after S255IR NIRS3, NGC 6334I-MM1, and G358.93−0.03-MM1. G24.33+0.14 is unique among these sources as it clearly shows a repeating flare with an 8 yr interval. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we observed the millimeter continuum and molecular lines toward G24.33+0.14 in the pre-flare phase in 2016 August (ALMA Cycle 3) and the mid-flare phase in 2019 September (ALMA Cycle 6). We identified three continuum sources in G24.33+0.14, and the brightest source, C1, which is closely associated with the 6.7 GHz maser emission, shows only a marginal increase in flux density with a flux ratio (Cycle 6$/$Cycle 3) of 1.16 ± 0.01, considering an additional absolute flux calibration uncertainty of $10\%$. We identified 26 transitions from 13 molecular species other than methanol, and they exhibit similar levels of flux differences with an average flux ratio of 1.12 ± 0.15. In contrast, eight methanol lines observed in Cycle 6 are brighter than those in Cycle 3 with an average flux ratio of 1.23 ± 0.13, and the higher excitation lines tend to show a larger flux increase. If this systematic increasing trend is real, it would suggest radiative heating close to the central HMYSO due to an accretion event which could expand the size of the emission region and/or change the excitation conditions. Given the low brightness temperatures and small flux changes, most of the methanol emission is likely to be predominantly thermal, except for the 229.759 GHz (8−1–70E) line known as a class I methanol maser. The flux change in the millimeter continuum of G24.33+0.14 is smaller than in S255IR NIRS3 and NGC 6334I-MM1 but is comparable with that in G358.93−0.03-MM1, suggesting different amounts of accreted mass in these events.

Compared with guidelines, supersonic shear imaging liver stiffness dual threshold values of less than 7 kPa and greater than 12 kPa were close to target sensitivity and specificity for compensated advanced chronic liver disease in high-risk patients.

Two-photon polymerization (TPP) currently offers the highest resolution available in 3D printing (∼100 nm) but requires femtosecond laser pulses at very high peak intensity (∼1 TW/cm2). Here, we demonstrate 3D printing based on triplet–triplet-annihilation photopolymerization (TTAP), which achieves submicron resolution while using a continuous visible LED light source with comparatively low light intensity (∼10 W/cm2). TTAP enables submicrometer feature sizes with exposure times of ∼0.1 s/voxel without requiring a coherent or pulsed light source, opening the door to low-cost fabrication with submicron resolution. This approach enables 3D printing of a diverse array of designs with high resolution and is amenable to future parallelization efforts.

Fresh sweet corn is vulnerable to microbial damage and difficult to preservation at ambient temperature due to the high water and sugar contents. Therefore, in the present study, fresh sweet corn kernels were subjected to hot air drying (HAD), vacuum freeze drying (VFD), microwave drying (MD), and short‐ and medium‐wave infrared drying (SMIRD). Different drying ways of dehydrated sweet corns were compared in terms of physical properties, nutritional components, volatile compounds, and antioxidant capacity. After thermal treatment, sweet corn will form more volatile components and increase the flavor of sweet corn, while sweet corn treated by VFD will lose a lot of volatile components and weaken the flavor. The results demonstrated that VFD products exhibited higher rehydration capacity, more nutrient retention, and better antioxidant capacity with fewer volatile compounds. A total of 63 different volatile compounds were detected in dried sweet corns. The variety of volatile substances was the maximum in the SMIRD (55), followed by HAD (35), MD (28), fresh (22), and VFD (9). Overall, this study would be fundamental for selecting more applicable drying methods to obtain desirable quality of dried sweet corn.

The loess produced in South Korea is an eco-friendly material with high gas adsorption performance. Korean loess, however, cannot be used as a structural material because it has a very low compressive strength compared to cement. However, even if it is recommended as an interior material, its large drying shrinkage during drying disturbs wet construction. Therefore, this study aimed to develop a method to reduce the amount of water added while maintaining the consistency required for the plastering work of Korean loess. The experimental results showed that the dispersion of clay particles was improved when Na+ and K+, which are monovalent cations, were added to the loess colloid; the reverse occurred, i.e., aggregation of clay particles, when Ca2+ and Mg2+, which are divalent cations, were added. In addition, the dispersion and aggregation of clay particles affect the consistency of loess. The dispersion allows the loess paste to obtain the required consistency using less water, but the aggregation may exhibit the opposite effect. Accordingly, based on the same consistency, the specimens with less water exhibited less drying shrinkage. The drying shrinkage decreased by 9.23% for the specimen fabricated with the 0.01 M Na2SiO3 aqueous solution.

Extracellular vesicles (EVs) have emerged as biocompatible nanocarriers for efficient delivery of various therapeutic agents, with intrinsic long-term blood circulatory capability and low immunogenicity. Here, indocyanine green (ICG)- and paclitaxel (PTX)-loaded EVs [EV(ICG/PTX)] were developed as a biocompatible nanoplatform for safe and efficient cancer treatment through near-infrared (NIR) light-triggered combination chemo/photothermal/photodynamic therapy. High dual drug encapsulation in EVs was achieved for both the hydrophilic ICG and hydrophobic PTX by simple incubation. The EVs substantially improved the photostability and cellular internalization of ICG, thereby augmenting the photothermal effects and reactive oxygen species production in breast cancer cells upon NIR light irradiation. Hence, ICG-loaded EVs activated by NIR light irradiation showed greater cytotoxic effects than free ICG. EV(ICG/PTX) showed the highest anticancer activity owing to the simultaneous chemo/photothermal/photodynamic therapy when compared with EV(ICG) and free ICG. In vivostudy revealed that EV(ICG/PTX) had higher accumulation in tumors and improved pharmacokinetics compared to free ICG and PTX. In addition, a single intravenous administration of EV(ICG/PTX) exhibited a considerable inhibition of tumor proliferation with negligible systemic toxicity. Thus, this study demonstrates the potential of EV(ICG/PTX) for clinical translation of combination chemo-phototherapy.