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Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory and fibrotic response-driven lung disease that is difficult to cure because it manifests excessive profibrotic cytokines (e.g., TGF-β), activated myofibroblasts, and accumulated extracellular matrix (ECM). In an attempt to develop an inhalation formulation with enhanced antifibrotic efficacy, we sought to fabricate unique aerosolizable inhaled microgels (μGel) that contain nintedanib-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs; n-PN) and pirfenidone-liposomes (p-LP). The aero-μGel was ∼12 μm, resisted phagocytosis by alveolar macrophages in vitro and in vivo, and protected inner-entrapped n-PN and p-LP. The n-PN/p-LP@aero-μGel caused enhanced/extended antifibrotic efficacy in a bleomycin-induced pulmonary fibrosis mouse presumably due to prolonged lung residence. Consequently, the results obtained by intratracheal aerosol insufflation of our n-PN/p-LP@aero-μGel twice a week were much better than those by as many as seven doses of single or mixed applications of n-PN or p-LP. The antifibrotic/pharmacokinetic results for the n-PN/p-LP@aero-μGel included reduced fibrosis progression, restored lung physiological functions, deactivated myofibroblasts, inhibited TGF-β progression, and suppressed ECM component production (collagen I and α-SMA) along with prolonged lung retention time. We believe that our n-PN/p-LP@aero-μGel increased the local availability of both nintedanib and pirfenidone due to evasion of alveolar macrophage phagocytosis and prolonged lung retention with reduced systemic distribution. Through this approach, our inhalation formulation subsequently attenuated fibrosis progression and improved lung function. Importantly, these results hold profound implications in the therapeutic potential of our n-PN/p-LP@aero-μGel to serve as a clinically promising platform, providing significant advancements for improved treatment of many respiratory diseases including IFP.

Abstract This paper presents the first scanning electron microscopy (SEM)‐based DNA imaging in biological samples. This novel approach incorporates a metal‐free electro‐stain reagent, formulated by combining DNA‐binding proteins and synthetic polymers to enhance the visibility of 2‐nm‐thick DNA under SEM. Notably, DNA molecules stain with proteins and polymers appear as dark lines under SEM. The resulting DNA images exhibit a thickness of 15.0±4.0 nm. As SEM is the primary platform, it integrates seamlessly with various chemically functionalized large surfaces with the aid of microfluidic devices. The approach allows high‐resolution imaging of various DNA structures including linear, circular, single‐stranded DNA and RNA, originating from nuclear and mitochondrial genomes. Furthermore, quantum dots are successfully visualized as bright labels that are sequence‐specifically incorporated into DNA molecules, which highlights the potential for SEM‐based optical DNA mapping. In conclusion, DNA imaging using SEM with the novel electro‐stain offers electron microscopic resolution with the ease of optical microscopy.

Since battery systems typically account for over 40% of the cost of an electric vehicle, their mid-life replacements are exceptional. Therefore, the battery’s lifespan must exceed that of the vehicle. To ensure long-term and safe use, accurate state-of-charge (SOC) estimation must be maintained throughout the battery’s lifespan. This requires appropriate updates to parameters, such as capacity, in the battery model. In this context, dual extended Kalman filters, which simultaneously estimate both states and parameters, have gained interest. While existing reports on simultaneous estimators seemed promising, our study found that they performed well under low levels of battery aging but encountered issues at higher levels. Accurately reflecting the actual physicochemical changes of the parameters in aging cells is challenging for two reasons: the limited number of measurements of terminal voltage available for numerous parameters, and the weak observability of the capacity. Therefore, we combined the simultaneous estimator with a capacity estimator operated separately during charging and a sequential estimator specialized for an enhanced self-correcting model, achieving SOC accuracy within 5% even when the SOH decreased by 30%. However, there is still much work to be carried out to implement sequential estimators in battery management systems operating in real time with limited computational resources.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.

Abstract In this study, we demonstrate that a digital colorimetric sensor platform can transform a conventional energy system, such as gas‐insulated switchgear (GIS) into a smart green energy system. Our sensor platform consists of a colorimetric sensor film (CSF), an array of silicon photodiodes, and a low‐power‐driven fiber optical photodiode with a wireless communication protocol integrated into an information network. The photodiode measures the transmitted light of the color‐variable CSF when exposed to sulfur dioxide (SO2) gas, a decomposition by‐product of the sulfur hexafluoride (SF6) gas in GIS. We report the electrical photocurrent measurement through the CSF can measure the concentration of SO2 gas via remote and real‐time monitoring and shows a comparable behavior to UV–Vis absorption measurement. The limit of detection of the sensor, 0.78 ppm is sufficient to analyze the GIS insulation deterioration allowing green energy systems.

Owing to their unique optical and chemical properties, gold nanorods (AuNRs) are among the most frequently used nanomaterials for biomedical applications, including cancer therapy, imaging, and drug delivery. In particular, the longitudinal dipole plasmon wavelength of AuNRs can be verified from the visible to the near‐infrared (NIR) region, allowing AuNRs to be used as photodynamic/photothermal and imaging contrast agents. At the same time, the silica shell is important as it enhances stability and facilitates the functionalization and biocompatibility of AuNRs, offering numerous advantages in biomedical applications. In this review, silica‐coated AuNRs from a bioapplication perspective are focused. First, the importance of AuNRs for biomedical applications is explained and the purpose of silica coating on AuNRs is discussed. Then, recent studies on the development of silica‐coated AuNRs from a biomedical perspective are reviewed. Subsequently, various strategies for engineering silica coatings and their properties in the biomedical field are reviewed. This review is expected to promote further research on next‐generation silica‐coated AuNRs for biomedical applications.

Abstract Background Bone regeneration research is currently ongoing in the scientific community. Materials approved for clinical use, and applied to patients, have been developed and produced. However, rather than directly affecting bone regeneration, these materials support bone induction, which regenerates bone. Therefore, the research community is still researching bone tissue regeneration. In the papers published so far, it is hard to find an improvement in the theory of bone regeneration. This review discusses the relationship between the existing theories on hard tissue growth and regeneration and the biomaterials developed so far for this purpose and future research directions. Mainbody Highly complex nucleation and crystallization in hard tissue involves the coordinated action of ions and/or molecules that can produce different organic and inorganic composite biomaterials. In addition, the healing of bone defects is also affected by the dynamic conditions of ions and nutrients in the bone regeneration process. Inorganics in the human body, especially calcium- and/or phosphorus-based materials, play an important role in hard tissues. Inorganic crystal growth is important for treating or remodeling the bone matrix. Biomaterials used in bone tissue regeneration require expertise in various fields of the scientific community. Chemical knowledge is indispensable for interpreting the relationship between biological factors and their formation. In addition, sources of energy for the nucleation and crystallization processes of such chemical bonds and minerals that make up the bone tissue must be considered. However, the exact mechanism for this process has not yet been elucidated. Therefore, a convergence of broader scientific fields such as chemistry, materials, and biology is urgently needed to induce a distinct bone tissue regeneration mechanism. Conclusion This review provides an overview of calcium- and/or phosphorus-based inorganic properties and processes combined with organics that can be regarded as matrices of these minerals, namely collagen molecules and collagen fibrils. Furthermore, we discuss how this strategy can be applied to future bone tissue regenerative medicine in combination with other academic perspectives.

Electron microscopy‐based DNA imaging is a powerful tool that provides a high resolution for observing genomic structures involved in biochemical processes. The first method, heavy metal shadow casting, was developed in 1948. Uranyl acetate has been widely used for DNA electron microscopic imaging since the 1960s. However, for this method, scientists must deal with government regulations for the safety and disposal. Additionally, sample preparation is often complicated and time‐consuming. Recently, nanoparticles and nanowires have emerged as a new way of imaging DNA molecules under both transmission and scanning electron microscopes. However, as this technology is still in its early stages, there is room for further development. In this review, heavy metal staining, nanoparticle staining, and nanowire growth for DNA visualization are introduced. The applications of shadow casting and uranyl acetate staining in the visualization of DNA structures and protein–DNA complexes are discussed. Then, nanomaterial‐based DNA staining methods are covered, including electrostatic interactions, DNA chain modification, reducing‐group‐modified DNA ligands and DNA–peptide/protein interactions. This review provides up‐to‐date information on different DNA staining approaches and their applications in DNA studies. Ultimately, it offers a new direction for genome analysis through DNA visualization.

Abstract Mineralized fibrils are important building blocks in bone tissue, formed by the hierarchical assembly of collagen molecules and crystalline hydroxyapatite (HAp). The mineralization pathway of HAp is reported as a nonclassical‐crystallization, but the nanoconfined crystallization in collagen fibrils remains poorly understood. The mechanism of intrafibrillar mineralization of collagen‐PDA fibrils in modified‐simulated body fluid (m‐SBF) solution is studied. Collagen‐amorphous calcium phosphate (ACP) fibrils are obtained by assembling collagen‐PDA fibrils with polyaspartic acid (pAsp) as a stabilizer. The ACP undergoes a phase transformation to HAp within the fibrils upon adjusting the phosphate concentration. It is found that the phase transformation of ACP to HAp in collagen fibrils can be accelerated with a 12 h incubation with 1/10 ratio of Ca2+ to [PO4]3−. A lower ratio of 1/1 and 1/5 results in a much slower phase transformation. This finding suggests that an elevated concentration of [PO4]3− is crucial for faster phase transformation. The relationship between the crystallization rate of HAp in the fibrils and the degree of mineralization is found to be linear in all cases, indicating an interface‐controlled process. This gives a better understanding of the mechanism of HAp mineralization in collagen fibrils, providing an effective approach to material design.

Abstract Rapid industrial growth has severely impacted ecosystems and aggravated economic and health risks to society. Monitoring of ecosystems is fundamental to our understanding of how ecosystem change impacts resources and is critical for developing data‐based sustainability. Thus, the design and development of optimized sensors for ecosystem monitoring have received increasing attention. This review provides a comprehensive overview of systematic sensor design strategies for ecosystem monitoring from the material level to the form factor level. We discuss the fundamental transducing mechanisms of a representative sensor system including optical, electrical, and electrochemical sensors. We then review the sensor interfacing strategy for achieving stable and real‐time monitoring of environmental biochemical factors from air, water, soil, and living organisms. Finally, we provide a summary of the current performance and prospects of this state‐of‐the‐art sensor technology and an outlook on opportunities for possible future research directions in this emerging field.

Abstract Background A considerable number of studies has been carried out to develop alloplastic bone graft materials such as hydroxyapatite (HAP) that mimic the hierarchical structure of natural bones with multiple levels of pores: macro-, micro-, and nanopores. Although nanopores are known to play many essential roles in natural bones, only a few studies have focused on HAPs containing them; none of those studies investigated the functions of nanopores in biological systems. Method We developed a simple yet powerful method to introduce nanopores into alloplastic HAP bone graft materials in large quantities by simply pressing HAP nanoparticles and sintering them at a low temperature. Results The size of nanopores in HAP scaffolds can be controlled between 16.5 and 30.2 nm by changing the sintering temperature. When nanopores with a size of ~ 30.2 nm, similar to that of nanopores in natural bones, are introduced into HAP scaffolds, the mechanical strength and cell proliferation and differentiation rates are significantly increased. The developed HAP scaffolds containing nanopores (SNPs) are biocompatible, with negligible erythema and inflammatory reactions. In addition, they enhance the bone regeneration when are implanted into a rabbit model. Furthermore, the bone regeneration efficiency of the HAP-based SNP is better than that of a commercially available bone graft material. Conclusion Nanopores of HAP scaffolds are very important for improving the bone regeneration efficiency and may be one of the key factors to consider in designing highly efficient next-generation alloplastic bone graft materials.

Extensive research is focused on the development of highly sensitive, rapid on-site diagnostic devices. The lateral flow strip (LFS) is a paper-based point-of-care diagnostic device, which is highly promising because of its ease of use and low cost. Despite these advantages, LFS device is still less popular than other methods such as enzyme-linked immunosorbent assay (ELISA) or real-time polymerase chain reaction (qPCR) due to its low sensitivity. Here, we have developed a fluorescence-based lateral flow strip (f-LFS) device for DNA detection using a molecular beacon (MB), a short hairpin-forming DNA strand tagged with a fluorophore-quencher pair. Each paper and membrane component of f-LFS device was carefully selected based on their physicochemical properties including porosity, surface functionality, and autofluorescence. The limit of detection (LOD) of this device was substantially improved to 2.1 fg/mL by adding MgCl2 to the reaction buffer and narrowing the test membrane dimension. Also, a portable fluorescence detection system for f-LFS was developed using a multi-pixel photon counter (MPPC), a sensitive detector detecting the signal on site. We anticipate that this highly sensitive paper-based diagnostic device can be utilized for on-site diagnosis of various diseases.

This paper proposes a framework for accurately estimating the state-of-charge (SOC) and current sensor bias, with the aim of integrating it into urban air mobility (UAM) with hybrid propulsion. Considering the heightened safety concerns in an airborne environment, more reliable state estimation is required, particularly for the UAM that uses a battery as its primary power source. To ensure the suitability of the framework for the UAM, a two-pronged approach is taken. First, realistic test profiles, reflecting actual operational scenarios for the UAM, are used to model the battery and validate its state estimator. These profiles incorporate variations in battery power flow, namely, charge-depleting and charge-sustaining modes, during the different phases of the UAM’s flight, including take-off, cruise, and landing. Moreover, the current sensor bias is estimated and corrected concurrently with the SOC. An extended Kalman filter-based bias estimator is developed and experimentally validated using actual current measurements from a Hall sensor, which is prone to noise. With this correction, a SOC estimation error is consistently maintained at 2% or lower, even during transitions between operational modes.

Abstract In this research, dispersion of a new type of one-dimensional inorganic material Nb2Se9, composed of van der Waals bonds, in aqueous solution for bio-application study were studied. To disperse Nb2Se9, which exhibits hydrophobic properties in water, experiments were carried out using a block copolymer (poloxamer) as a dispersant. It was confirmed that PPO, the hydrophobic portion of Poloxamer, was adsorbed onto the surface of Nb2Se9, and PEO, the hydrophilic portion, induced steric hinderance to disperse Nb2Se9 to a size of 10 nm or less. To confirm the adaptability of muscle cells C2C12 to the dispersed Nb2Se9 using poloxamer 188 as dispersant, a MTT assay and a live/dead assay were performed, demonstrating improvement in the viability and proliferation of C2C12 cells.

Background and Objectives Hizikia fusiformis is widely used in oriental health food in Japan, China, and Korea, and is known for its anti-oxidation properties. Materials and Method In this study, we investigated the anti-inflammatory and immune-modulatory effects and mechanisms of Hizikia fusiformis (H. fusiformis) extracts in lipopolysaccharide (LPS)-treated RAW 264.7 cells. RAW 264.7 cells were incubated in the presence of different concentrations of the viscozyme component of H. fusiformis (1, 2, 5, and 10 μg/mL), and changes in expression of pro-inflammatory cytokines (GM-CSF, iNOS, VEGF, and COX-2) were evaluated by real-time PCR and immunoblotting. In addition, the associated signaling pathway including phospho (p)-pNF-κB 65, p-pIkBa, p-p38, and p-p44/42 was also evaluated. Results The viscozyme component of H. fusiformis downregulated the expression of GM-CSF, iNOS, VEGF, and COX-2 mRNA. The augmented NO and ROS production was decreased by administration of H. fusiformis. The signal intensity of p-pNF-κB 65, p-pIkBa, p-p38, and p-p44/42 protein activated by LPS was ameliorated by administration of the viscozyme fraction in RAW 264.7 cells. Conclusion These results suggest that H. fusiformis has potential as a therapeutic agent for inflammatory diseases.

The antimicrobial activity of acetone, hexane, dichloromethane, and methanol extracts from leaves, stems, immature green fruits, and red fruits of tomato plants was examined against six phytopathogens. The minimum inhibitory concentration (MIC) of the acetonic extracts from these four plant parts was lower than that of the other solvents. Among the acetonic extracts, tomato leaves had a lower MIC than the other tomato parts. The acetonic extract from tomato leaves was therefore selected as a source of antimicrobial substances. The acetonic extract from tomato leaves inhibited mycelial growth of Fusarium oxysporum f. sp. lycopersici, Glomerella cingulata, and Rhizoctonia solani. Mycelial growth of R. solani treated with acetone extract from leaves showed more susceptibility than the other phytopathogens. Using 0.31 mg/ml of the acetonic extract from leaves, mycelial growth of R. solani on days 1, 2, and 3 decreased by 50.0, 52.1, and 64.0%, respectively, compared with acetone solvent treatment. The antimicrobial compounds effective against R. solani were identified as linolenic acid and caffeic acid by bioautography and GC-MS. These two compounds were used to treat six phytopathogens to confirm their antimicrobial activities. Linolenic acid inhibited mycelial growth of R. solani, while caffeic acid showed only slight antimicrobial activity. Results : indicated that we propose extracts from tomato leaves which included antimicrobial compounds may provide a new lead in the pursuit of new biological sources of agrochemical candidates.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The tailored manipulation of ceramic surfaces gained recent interest to optimize the performance and lifetime of composite materials used as implants. In this work, a hierarchical surface texturing of hydroxyapatite (HAp) ceramics was developed to improve the poor adhesive bonding strength in hydroxyapatite and polycaprolactone (HAp/PCL) composites. Four different types of periodic surface morphologies (grooves, cylindric pits, linear waves and Gaussian hills) were realized by a ceramic micro-transfer molding technique in the submillimeter range. A subsequent surface roughening and functionalization on a micron to nanometer scale was obtained by two different etchings with hydrochloric and tartaric acid. An ensuing silane coupling with 3-aminopropyltriethoxysilane (APTES) enhanced the chemical adhesion between the HAp surface and PCL on the nanometer scale by the formation of dipole–dipole interactions and covalent bonds. The adhesive bonding strengths of the individual and combined surface texturings were investigated by performing single-lap compressive shear tests. All individual texturing types (macro, micro and nano) showed significantly improved HAp/PCL interface strengths compared to the non-textured HAp reference, based on an enhanced mechanical, physical and chemical adhesion. The independent effect mechanisms allow the deliberately hierarchical combination of all texturing types without negative influences. The hierarchical surface-textured HAp showed a 6.5 times higher adhesive bonding strength (7.7 ± 1.5 MPa) than the non-textured reference, proving that surface texturing is an attractive method to optimize the component adhesion in composites for potential medical implants.

In biological systems, a few sequence differences diversify the hybridization profile of nucleotides and enable the quantitative control of cellular metabolism in a cooperative manner. In this respect, the information required for a better understanding may not be in each nucleotide sequence, but representative information contained among them. Existing methodologies for nucleotide sequence design have been optimized to track the function of the genetic molecule and predict interaction with others. However, there has been no attempt to extract new sequence information to represent their inheritance function. Here, we tried to conceptually reveal the presence of a representative sequence from groups of nucleotides. The combined application of the K-means clustering algorithm and the social network analysis theorem enabled the effective calculation of the representative sequence. First, a “common sequence” is made that has the highest hybridization property to analog sequences. Next, the sequence complementary to the common sequence is designated as a ‘representative sequence’. Based on this, we obtained a representative sequence from multiple analog sequences that are 8–10-bases long. Their hybridization was empirically tested, which confirmed that the common sequence had the highest hybridization tendency, and the representative sequence better alignment with the analogs compared to a mere complementary.