Graphene Hybrid Tough Hydrogels with Nanostructures for Tissue Regeneration.

Over the past few decades, hydrogels have attracted considerable attention as promising biomedical materials. However, conventional hydrogels require improved mechanical properties, such as brittleness, which significantly limits their widespread use. Recently, hydrogels with remarkably improved toughness have been developed; however, their low biocompatibility must be addressed. In this study, we developed a tough graphene hybrid hydrogel with nanostructures. The resultant hydrogel exhibited remarkable mechanical properties while representing an aligned nanostructure that resembled the extracellular matrix of soft tissue. Owing to the synergistic effect of the topographical properties, and the enhanced biochemical properties, the graphene hybrid hydrogel had excellent stretchability, resilience, toughness, and biocompatibility. Furthermore, the hydrogel displayed outstanding tissue regeneration capabilities (e.g., skin and tendons). Overall, the proposed graphene hybrid tough hydrogel may provide significant insights into the application of tough hydrogels in tissue regeneration.

Gelatin Nanoparticles can Improve Pesticide Delivery Performance to Plants.

Nanomaterials associated with plant growth and crop cultivation revolutionize traditional concepts of agriculture. However, the poor reiterability of these materials in agricultural applications necessitates the development of environmentally-friendly approaches. To address this, biocompatible gelatin nanoparticles (GNPs) as nanofertilizers with a small size (≈150 nm) and a positively charged surface (≈30 mV) that serve as a versatile tool in agricultural practices is designed. GNPs load agrochemical agents to improve maintenance and delivery. The biocompatible nature and small size of GNPs ensure unrestricted nutrient absorption on root surfaces. Furthermore, when combined with pesticides, GNPs demonstrate remarkable enhancements in insecticidal (≈15%) and weed-killing effects (≈20%) while preserving the efficacy of the pesticide. That GNPs have great potential for use in sustainable agriculture, particularly in inducing plant growth, specifically plant root growth, without fertilization and in enhancing the functions of agrochemical agents is proposed. It is suggested conceptual applications of GNPs in real-world agricultural practices.

Micro/nanoengineered agricultural by-products for biomedical and environmental applications.

Agriculturally derived by-products generated during the growth cycles of living organisms as secondary products have attracted increasing interest due to their wide range of biomedical and environmental applications. These by-products are considered promising candidates because of their unique characteristics including chemical stability, profound biocompatibility and offering a green approach by producing the least impact on the environment. Recently, micro/nanoengineering based techniques play a significant role in upgrading their utility, by controlling their structural integrity and promoting their functions at a micro and nano scale. Specifically, they can be used for biomedical applications such as tissue regeneration, drug delivery, disease diagnosis, as well as environmental applications such as filtration, bioenergy production, and the detection of environmental pollutants. This review highlights the diverse role of micro/nano-engineering techniques when applied on agricultural by-products with intriguing properties and upscaling their wide range of applications across the biomedical and environmental fields. Finally, we outline the future prospects and remarkable potential that these agricultural by-products hold in establishing a new era in the realms of biomedical science and environmental research.

Graphene Hybrid Inner Ear Organoid with Enhanced Maturity.

Inner ear organoids (IEOs) are 3D structures grown in vitro, which can mimic the complex cellular structure and function of the inner ear. IEOs are potential solutions to problems related to inner ear development, disease modeling, and drug delivery. However, current approaches in generating IEOs using chemical factors have a few limitations, resulting in unpredictable outcomes. In this study, we propose the use of nanomaterial-based approaches, specifically by using graphene oxide (GO). GO's unique properties promote cell-extracellular matrix interactions and cell-cell gap junctions, thereby enhancing hair cell formation, which is an essential part of IEO development. We also investigated the potential applications for drug testing. Our findings suggest that GO is a promising candidate for enhancing the functionality of IEOs and advancing our understanding of the problems underlying inner ear development. The use of nanomaterial-based approaches may provide a more reliable and effective method for building better IEOs in the future.

Biodegradable and Flexible Nanoporous Films for Design and Fabrication of Active Food Packaging Systems.

Nanotechnology has facilitated the development of active food packaging systems with functions that could not be achieved by their traditional counterparts. Such smart and active systems can improve the shelf life of perishable products and overcome major bottlenecks associated with the fabrication of safe and environmentally friendly food packaging systems. Herein, we used a plasma-enabled surface modification strategy to fabricate biodegradable and flexible nanoporous polycaprolactone-based (FNP) films for food packaging systems. Their capacity for preserving tomatoes, tangerines, and bananas at room and refrigeration temperatures was tested by analyzing various fruit parameters (mold generation, appearance changes, freshness, weight loss, firmness, and total soluble solids contents). Compared with commonly used polyethylene terephthalate-based containers, the proposed system enhanced the fruit storage quality (i.e., retained appearance, reduced weight loss, better firmness, and sugar contents) by controlling moisture evaporation and inhibiting mold generation. Thus, the FNP film represents a new active food packaging strategy.

Synthesis and structure-activity relationship studies of 1,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 1 (JAK1) inhibitors.

JAK inhibitors have been considered as useful targets for the treatment of related diseases. However, first-generation JAK inhibitors have side effects such as anemia, thrombocytopenia, neutropenia and headaches which have been suggested to result from high JAK2 inhibition. Second-generation JAK inhibitors with more specific JAK isozyme inhibition have been studied to eliminate these adverse effects. In this study, novel 4-(1,5- or 2,5-triazole)-pyrrolopyrimidine derivatives with aromatic moieties were synthesized as JAK1 inhibitors, and an in vitro enzyme assay was used to evaluate the JAK inhibitory effects. Among these JAK1 inhibitors, the compound 23a showed an IC50 level of 72 nM, as well as being selective against other JAKs by 12 times or more: the results of molecular docking studies suggested that the high JAK1 selectivity resulted from a key interaction between the iodine atom of compound 23a and His-885 of hJAK1.

Engineering plants with carbon nanotubes: a sustainable agriculture approach.

Sustainable agriculture is an important conception to meet the growing food demand of the global population. The increased need for adequate and safe food, as well as the ongoing ecological destruction associated with conventional agriculture practices are key global challenges. Nanomaterials are being developed in the agriculture sector to improve the growth and protection of crops. Among the various engineered nanomaterials, carbon nanotubes (CNTs) are one of the most promising carbon-based nanomaterials owing to their attractive physiochemical properties such as small size, high surface area, and superior mechanical and thermal strength, offering better opportunities for agriculture sector applications. This review provides basic information about CNTs, including their history; classification; and electrical, thermal, and mechanical properties, with a focus on their applications in the agriculture field. Furthermore, the mechanisms of the uptake and translocation of CNTs in plants and their defense mechanisms against environmental stresses are discussed. Finally, the major shortcomings, threats, and challenges of CNTs are assessed to provide a broad and clear view of the potential and future directions for CNT-based agriculture applications to achieve the goal of sustainability.

Striatal Dopamine D2 Receptor Occupancy Induced by Daily Application of Blonanserin Transdermal Patches: Phase II Study in Japanese Patients With Schizophrenia.

BACKGROUND: Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application. METHODS: This open-label, phase II study enrolled 18 Japanese outpatients (20 to <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2-4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2-4 weeks based on the oral dose. [11C]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global Impressions-Severity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness. RESULTS: Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D2 receptor occupancy for blonanserin tablets 8 mg/d (59.2%, n = 5) and 16 mg/d (66.3%, n = 9) was within the values for blonanserin patches: 10 mg/d (33.3%, n = 3), 20 mg/d (29.9%, n = 2), 40 mg/d (61.2%, n = 3), 60 mg/d (59.0%, n = 3), and 80 mg/d (69.9%, n = 3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/d and 31.9 mg/d, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns. CONCLUSIONS: Blonanserin patches (40/80 mg/d) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/d), and patches at doses of 40 mg/d and 80 mg/d appear to be a suitable alternative for blonanserin tablets at doses of 8 mg/d and 16 mg/d, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia. TRIAL REGISTRY: JAPIC Clinical Trials Information registry (www.clinicaltrials.jp; JapicCTI-No: JapicCTI-121914).

Eggshell membrane as a bioactive agent in polymeric nanotopographic scaffolds for enhanced bone regeneration.

A bone regeneration scaffold is typically designed as a platform to effectively heal a bone defect while preventing soft tissue infiltration. Despite the wide variety of scaffold materials currently available, such as collagen, critical problems in achieving bone regeneration remain, including a rapid absorption period and low tensile strength as well as high costs. Inspired by extracellular matrix protein and topographical cues, we developed a polycaprolactone-based scaffold for bone regeneration using a soluble eggshell membrane protein (SEP) coating and a nanotopography structure for enhancing the physical properties and bioactivity. The scaffold exhibited adequate flexibility and mechanical strength as a biomedical platform for bone regeneration. The highly aligned nanostructures and SEP coating were found to regulate and enhance cell morphology, adhesion, proliferation, and differentiation in vitro. In a calvaria bone defect mouse model, the scaffolds coated with SEP applied to the defect site promoted bone regeneration along the direction of the nanotopography in vivo. These findings demonstrate that bone-inspired nanostructures and SEP coatings have high potential to be applicable in the design and manipulation of scaffolds for bone regeneration.

Observability Study on Passive Target Localization by Conic-Angle Measurements.

Information from a passive linear array sensor is related to the conic angle formed by a target and the sensor in three-dimensional (3D) space so that the target localization system using the sensor should be also designed in 3D space. This paper presents an observability study of a passive target localization system created using conic angle information. The study includes the analysis of the sensor maneuver requirement needed to achieve system observability and simulations to demonstrate the results of the analytic scheme. The proposed sensor maneuver requirements satisfy the system observability conditions by using the local linearization approach of the Fisher information matrix. It is also shown that this requirement can be mitigated for special cases in which the depth difference between the sensor and the target is given. Using the simulation, it is shown that sensors following the proposed scheme are able to obtain meaningful information that can be used to estimate 3D target states.

An Indexing Method of Continuous Spatiotemporal Queries for Stream Data Processing Rules of Detected Target Objects.

Real-time performance is important in rule-based continuous spatiotemporal query processing for risk analysis and decision making of target objects collected by sensors of combat vessels. The existing Rete algorithm, which creates a compiled node link structure for executing rules, is known to be the best. However, when a large number of rules are to be processed and the stream data to be performed are large, the Rete technique has an overhead of searching for rules to be bound. This paper proposes a hashing indexing technique for Rete nodes to the overhead of searching for spatiotemporal condition rules that must be bound when rules are expressed in a node link structure. A performance comparison evaluation experiment was conducted with Drool, which implemented the Rete method, and the method that implemented the hash index method presented in this paper. For performance measurement, processing time was measured for the change in the number of rules, the change in the number of objects, and the distribution of objects. The hash index method presented in this paper improved performance by at least 18% compared to Drool.

Low dopamine transporter binding in the nucleus accumbens in geriatric patients with severe depression.

AIM: Dysfunction of dopaminergic neurons in the central nervous system is considered to be related to major depressive disorder (MDD). Especially, MDD in geriatric patients is characterized by anhedonia, which is assumed to be associated with reduced dopamine neurotransmission in the reward system. Dopamine transporter (DAT) is considered to reflect the function of the dopamine nerve system. However, previous DAT imaging studies using single photon emission computed tomography or positron emission tomography (PET) have shown inconsistent results. The radioligand [18 F]FE-PE2I for PET enables more precise evaluation of DAT availability. Hence, we aimed to evaluate the DAT availability in geriatric patients with MDD using [18 F]FE-PE2I. METHODS: Eleven geriatric patients with severe MDD and 27 healthy controls underwent PET with [18 F]FE-PE2I, which has high affinity and selectivity for DAT. Binding potentials (BPND ) in the striatum (caudate and putamen), nucleus accumbens (NAc), and substantia nigra were calculated. BPND values were compared between MDD patients and healthy controls. RESULTS: MDD patients showed significantly lower DAT BPND in the NAc (P = 0.009), and there was a trend of lower BPND in the putamen (P = 0.032) compared to controls. CONCLUSION: We found low DAT in the NAc and putamen in geriatric patients with severe MDD, which could be related to dysregulation of the reward system.

Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO.

Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results: Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

Nanopatterned Scaffolds for Neural Tissue Engineering and Regenerative Medicine.

Biologically inspired approaches employing nanoengineering techniques have been influential in the progress of neural tissue repair and regeneration. Neural tissues are exposed to complex nanoscale environments such as nanofibrils. In this chapter, we summarize representative nanotechniques, such as electrospinning, lithography, and 3D bioprinting, and their use in the design and fabrication of nanopatterned scaffolds for neural tissue engineering and regenerative medicine. Nanotopographical cues in combination with other cues (e.g., chemical cues) are crucial to neural tissue repair and regeneration using cells, including various types of stem cells. Production of biologically inspired nanopatterned scaffolds may encourage the next revolution for studies aiming to advance neural tissue engineering and regenerative medicine.

Repetitive element signature-based visualization, distance computation, and classification of 1766 microbial genomes.

The genomes of living organisms are populated with pleomorphic repetitive elements (REs) of varying densities. Our hypothesis that genomic RE landscapes are species/strain/individual-specific was implemented into the Genome Signature Imaging system to visualize and compute the RE-based signatures of any genome. Following the occurrence profiling of 5-nucleotide REs/words, the information from top-50 frequency words was transformed into a genome-specific signature and visualized as Genome Signature Images (GSIs), using a CMYK scheme. An algorithm for computing distances among GSIs was formulated using the GSIs' variables (word identity, frequency, and frequency order). The utility of the GSI-distance computation system was demonstrated with control genomes. GSI-based computation of genome-relatedness among 1766 microbes (117 archaea and 1649 bacteria) identified their clustering patterns; although the majority paralleled the established classification, some did not. The Genome Signature Imaging system, with its visualization and distance computation functions, enables genome-scale evolutionary studies involving numerous genomes with varying sizes.

In vivo activity of modafinil on dopamine transporter measured with positron emission tomography and [¹8F]FE-PE2I.

Modafinil, a wake-promoting drug used to treat narcolepsy, is a dopamine transporter inhibitor and is said to have very low abuse liability; this, however, is still up for debate. We conducted a dopamine transporter (DAT) occupancy study with modafinil (200 or 300 mg) in ten healthy volunteers using positron emission tomography (PET) with [¹8F]FE-PE2I, a new PET radioligand with high affinity and selectivity for the dopamine transporter, to characterize its relation to abuse liability. Mean striatal DAT occupancies were 51.4% at 200 mg and 56.9% at 300 mg. There was a significant correlation between occupancy and plasma concentration, indicating dose dependency of DAT inhibition by modafinil in the striatum, and especially in the nucleus accumbens. This study showed that DAT occupancy by modafinil was close to that of methylphenidate, indicating that modafinil may be near the same level as methylphenidate in relation to abuse liability in terms of dopaminergic transmission.

Large interrelated clusters of repetitive elements (REs) and RE arrays predominantly represent reference mouse chromosome Y.

The vast majority of the mouse and human genomes consist of repetitive elements (REs), while protein-coding sequences occupy only ~3 %. It has been reported that the Y chromosomes of both species are highly populated with REs although at present, their complete sequences are not available in any public database. The recent update of the mouse genome database (Build 38.1) from the National Center for Biotechnology Information (NCBI) indicates that mouse chromosome Y is ~92 Mb in size, which is substantially larger than the ~16 Mb reported previously (Build 37.2). In this study, we examined how REs are arranged in mouse chromosome Y (Build 38.1) using REMiner-II, a RE mining program. A combination of diverse REs and RE arrays formed large clusters (up to ~28 Mb in size) and most of them were directly or inversely related. Interestingly, the RE population of human chromosome Y (NCBI Build 37.2-current) was less dense, and the RE/RE array clusters were not evident in comparison to mouse chromosome Y. The annotated gene loci were distributed in five different regions and most of them were surrounded by unique RE arrays. In particular, tandem RE arrays were embedded into the introns of two adjacent gene loci. The findings from this study indicate that the large and interrelated clusters of REs and RE arrays predominantly represent the unique organizational pattern of mouse chromosome Y. The potential interactions among the clusters, which are populated with various interrelated REs and RE arrays, may play a role in the structural configuration and function of mouse chromosome Y.

Dexmedetomidine-induced contraction involves c-Jun NH2 -terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta.

Vasoconstriction induced by dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist, mainly involves c-Jun NH2 -terminal kinase (JNK) phosphorylation in the isolated endothelium-denuded aorta. We carried out an in vitro study to determine the main arachidonic acid metabolic pathway that is involved in dexmedetomidine-induced JNK activation. Cumulative dexmedetomidine concentration-contractile response curves were generated in the endothelium-denuded rat aorta in the presence or absence of the following inhibitors: the JNK inhibitor SP600125, the phospholipase A2 inhibitor quinacrine dihydrochloride, the non-specific lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor AA-861, the dual 5-LOX and cyclooxygenase (COX) inhibitor phenidone, the non-specific COX inhibitor indomethacin, the cytochrome p450 epoxygenase inhibitor fluconazole, the COX-1 inhibitor SC-560, and the COX-2 inhibitor NS-398. The effect of the alpha-2 adrenoceptor inhibitor rauwolscine and other inhibitors, such as quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, indomethacin and the protein kinase C inhibitor GF 109203X, on dexmedetomidine-induced JNK phosphorylation was investigated in rat aortic vascular smooth muscle cells with western blotting. The effect of dexmedetomidine on 5-LOX and COX-2 expression was investigated in vascular smooth muscle cells. SP600125, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, rauwolscine and chelerythrine attenuated dexmedetomidine-induced contraction. Indomethacin slightly attenuated dexmedetomidine-induced contraction. Fluconazole and SC-560 had no effect on dexmedetomidine-induced contraction, whereas NS-398 attenuated contraction. SP600125, rauwolscine, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone and GF 109203X attenuated dexmedetomidine-induced JNK phosphorylation. 5-LOX and COX-2 were upregulated by dexmedetomidine. Thus, dexmedetomidine-induced alpha-2 adrenoceptor-mediated contraction is mediated mainly by 5-LOX and partially by COX-2, which leads to JNK phosphorylation.

REViewer: a tool for linear visualization of repetitive elements within a sequence query.

A species-specific population of arrangements of repetitive elements (REs), called RE arrays, exists in the human and mouse genomes. We developed an RE analytical tool, named REViewer, for visualizing RE occurrences within RE arrays and other genomic regions as an interactive line map. REViewer utilizes an RE reference library which is established with two RE types: 1) REMiner-generated undefined REs and 2) RepeatMasker-derived defined REs. RE occurrences within queries are visualized as a line map using these two RE types. The REViewer's controller provides analytical options, such as zoom, customization of axis unit, and RE type selection. The functionality of REViewer was evaluated using the human chromosome Y sequence. The REViewer is determined to be an efficient tool that facilitates visualization of up to 6000 REs in RE arrays and other genomic regions. The maximum query size is linked to the RE mining tools (e.g., REMiner, RepeatMasker), not to REViewer.

Foldable Metamaterial Absorber with Liquid Metal Printing on Paper.

Metamaterials, characterized by their unique artificial periodic structures, exhibit extraordinary abilities in controlling electromagnetic waves not found in natural materials. Metamaterial absorbers, for example, have been developed by patterning solid conductive materials on dielectric surfaces. However, the foldability limitations of solid conductors make them unsuitable as foldable metamaterial absorbers since they lose those desirable properties when folded. To address this challenge, various methods using liquid metals have emerged, but they either require often necessitate structural frames or are primarily suited for hard surfaces, limiting their foldability potential. This study proposes an innovative solution involving the deposition of liquid metal onto paper surfaces to overcome foldability constraints. We design a metamaterial absorber with a circular pattern using three sheets of printing paper bonded with a film, leveraging these adhesive properties of oxidized gallium-based liquid metal to waterproof agent coated printing paper while preventing adhesion to laser-printed toner surfaces. The experimental results show that this absorber achieves an absorption rate of more than 90% in the frequency range of 10.36-10.76 GHz while being insensitive to polarization and incidence angle. Surprisingly, our proposed absorber retains its excellent performance even after being folded and unfolded up to 50 times. This foldable metamaterial absorber made of liquid metal is a promising solution for electromagnetic wave management applications requiring flexibility and adaptability.