Tag: Tokyo University of Science

Physical systems known as “reservoirs” are designed to emulate neural networks and meet the need for improved computational efficiency and speed. Overcoming the previous issues with compatibility, performance, and integration of such reservoir systems, researchers from Japan have recently developed an ion-gating transistor with improved reservoir states and short-term memory capabilities based on redox reactions. This development opens us the possibility of utilizing redox-based ionic devices for high-performance neuromorphic computing.

With major breakthroughs in artificial intelligence, image recognition, and object detection, the field of computing has witnessed a remarkable revolution in recent times. Being a data-driven field, the efficient analysis and processing of large and complex datasets is of utmost importance in computing. To enhance the efficiency and speed of data-driven tasks, researchers are exploring the possibility of recognizing complex patterns and relationships inherent in the data for the development of high-performance “neuromorphic” computing technology. This cutting-edge approach aims to replicate the brain’s ability to process information in a parallel and interconnected manner. By doing so, it seeks to construct a network of nodes capable of transforming data into high-dimensional representations suitable for complex tasks like pattern recognition, prediction, and classification.

Physical reservoirs resembling neural networks receive and interact with input signals or data, and their constituent elements, namely neurons and their interconnections, dynamically change over time. These reservoir states represent the physical system at a specific point and play a vital role in transforming input signals into high-dimensional representations. Securing the high dimensionality of a physical reservoir to achieve a sufficiently large number of reservoir states is, however, a challenging task.

Now, in a study published in the journal Advanced Intelligent Systems, researchers from Japan led by Associate Professor Tohru Higuchi at Tokyo University of Science (TUS) have developed a redox reaction-based ion-gating reservoir (redox-IGR) that can achieve a record-high number of reservoir states. With this development, Dr. Higuchi, along with Mr. Tomoki Wada and Mr. Daiki Nishioka from TUS, and Dr. Takashi Tsuchiya and Dr. Kazuya Terabe from National Institute for Materials Science (NIMS), Japan, have now advanced the possibility of translating higher-performance neuromorphic computing technology into a reality.

Ion-gating reservoirs consist of gate, drain, and source electrodes and are separated by an electrolyte that acts as a medium to control the flow of ions. Applying a voltage to the gate electrode triggers a redox reaction within the channel connecting the source and drain electrodes, resulting in a drain current that can be precisely modulated. Converting the time-series datasets into gate voltages can thus allow the corresponding output currents to serve as distinct reservoir states.

In this study, the researchers used lithium (Li+) ion conducting glass ceramic (LICGC) as an electrolyte. In LICGC, the Li+ ions travel faster compared to the channel, leading to the generation of two output currents — the drain current and an additional gate current, effectively doubling the number of reservoir states. Moreover, the different rates of ion transport in the channel and the electrolyte results in a delay in response of the drain current compared to the gate current. This delayed response enables short-term memory capabilities within the system, allowing the reservoir to retain and utilize information from past inputs, a crucial requirement for physical reservoirs.

To fabricate this device, the researchers deposited a 200-nm thick film of lithium cobalt oxide (LiCoO2) onto a 0.15-mm thick LICGC substrate. The gate electrode was composed of a thin film of Li-ion/platinum (Pt), while Pt thin films were used for the drain and source electrodes. The channel connecting the drain and source electrodes consisted of a 100-nm thick tungsten (VI) oxide (WO3) thin film.

“We have successfully reproduced electrical characteristics similar to those of neural circuits by utilizing redox reactions induced by the insertion and desorption of Li+ ions into the LixWO3 thin film,” explains Dr. Higuchi.

Demonstrating remarkable capabilities, the device achieved a total of 40 reservoir states (20 from the drain current and 20 from the gate current). It outperformed other physical reservoirs such as memristors and spin torque devices when solving second-order nonlinear dynamic equations. Most notably, the nonlinearity, the short-term memory capabilities, and the high number of reservoir states enabled the device to make predictions with a low mean square prediction error of 0.163 in the second-order nonlinear autoregressive moving average (NARMA2) task — a benchmark test for evaluating the performance of a reservoir system in performing complex nonlinear operations and predicting the future value of a time-series input based on its past values of both input and output.

Explaining the real-life implications of this development, Dr. Higuchi concludes, “The developed system has the potential to become a general-purpose technology that will be implemented in a wide range of electronic devices including computers and cell phones in the future.”

Researchers show that fucosylated heparan sulfate, a branched acidic glycosaminoglycan, exhibits anticoagulating and neurite outgrowth-promoting activities

Marine invertebrates, including bivalve mollusks like scallops, are potential sources of heparin or highly sulfated glycosaminoglycans (GAGs) with biological activities. Exploring them further, researchers from Japan and USA recently investigated the GAGs derived from the midgut gland of the Japanese scallop. They found that fucosylated heparan sulfate (Fuc-HS) from the midgut gland has anticoagulating and neurite outgrowth-promoting activities.

Glycosaminoglycans (GAGs), including chondroitin sulfate (CS), heparan sulfate (HS), heparin, and hyaluronan are linear and acidic polysaccharides found in the extracellular matrix of all animal tissues. GAGs are widely used as functional ingredients in health products, pharmaceuticals, and cosmetics, and are prepared from biological samples such as shark cartilage and porcine intestinal mucosa. Consequently, the demand for new sources of GAGs is ever-present. For example, the supply source of the anticoagulant heparin—generally prepared from porcine intestinal mucosa in China—was threatened by African swine fever in 2018.

GAGs derived from marine invertebrates—animals without a bony skeleton—such as bivalve mollusks are highly sulfated or branched with neutral sugars. These modifications enhance their properties and enable them to perform various biological activities. In fact, heparin-like polysaccharides with anticoagulant activity were identified from some kinds of bivalve mollusks.

In this light, a group of researchers led by Dr. Kyohei Higashi, Associate Professor at the Faculty of Pharmaceutical Sciences at the Tokyo University of Science (TUS), has investigated the structure and biological activities of GAGs derived from the midgut gland of the Japanese scallop, Patinopecten yessoensis, a bivalve mollusk.

Their work, made available online on 25th March 2023, will be published in Volume 313 of the Carbohydrate Polymers journal on 1st August 2023. It is co-authored by Dr. Takeshi Wada and Dr. Kazuki Sato of the TUS and Dr. Shinji Miyata of the Tokyo University of Agriculture and Technology.

Dr. Higashi briefly discusses the motivation behind the present research. “Scallops are among the most popular marine ingredients in Japan. While their adductor muscle and mantle are edible, their midgut gland, a potential cadmium accumulator, is usually discarded as waste during food processing. However, it may be a promising abundant source of GAGs, whose structures remain unexplored.”

In this study, the researchers extracted crude GAGs from the midgut gland of the Japanese scallop, fractionated them by anion exchange chromatography, and analyzed their structures through high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (1H NMR), and gas chromatography–mass spectrometry (GC–MS) techniques. HPLC revealed that HS, which showed resistance to GAG-degrading enzymes such as chondroitinases and heparinases, is the major GAG present in the gland. However, its resistance to heparinases decreased upon mild acid hydrolysis, hinting at the presence of the fucosyl (Fuc) group. 1H NMR confirmed the same. It detected significant signals corresponding to the H-6 methyl proton of Fuc and small signals corresponding to H-2 or H-3 of glucuronate (GlcA) present in HS, showing that Fuc is attached to the C-3 position of GlcA. Furthermore, GC–MS detected peaks corresponding to 1, 3, 5-tri-O-acetyl-2, 4-di-O-methyl-L-fucitol and 1, 4, 5-tri-O-acetyl-2, 3-di-O-methyl-L-fucitol, enabling researchers to conclude that Fuc is 3-O- or 4-O-sulfated.

Lastly, the study highlights that Fuc-HS shows biological activities such as anticoagulation or blood clot prevention and neurite—a projection from the nerve cell—outgrowth promotion. “These findings indicate that the midgut gland of scallops is a valuable source of Fuc-HS with novel functions. A more detailed investigation of the structure and biological activities of Fuc-HS might reveal its other potential applications, similar to the fucosylated chondroitin sulfate (Fuc-CS) that shows antiviral, anti-diabetic, anti-tumor, and immunomodulatory effects,” points out Dr. Higashi.

The researchers expect the present study to help facilitate the comprehensive analysis of the structure and functions of naturally occurring and biologically active GAGs derived from unutilized sources, which may provide hints for developing glycoside drugs.

Here’s hoping for the discovery of more novel GAGs![vc_single_image image=”36351″ img_size=”full” alignment=”center”]

Scientists have elucidated the reason for the new catalyst’s high activity, which is 2.1 times higher than commercial platinum nanoparticle-based catalysts

Hydrogen, derived from polymer electrolyte fuel cells (PEFCs), is an excellent source of clean energy. However, PEFCs require platinum (Pt), which is a limited resource. Some studies have shown that Pt nanoclusters (NCs) have higher activity than conventionally used Pt nanoparticles, however the origin of their higher activity is unclear. Now, researchers have synthesized a novel Pt NC catalyst with unprecedented activity and identified the reason for its high performance.

The twin issues of climate change and the shortage of fossil fuels are the new cornerstones challenges of energy research. Polymer electrolyte fuel cells (PEFCs), which produce the clean fuel hydrogen, are one of the most promising options to tackle both these challenges. However, PEFCs are expensive to make and operate, primarily because of the large amount of platinum (Pt) that they require. Moreover, the amount of Pt in the Earth’s crust is limited, which means that to make PEFCs truly sustainable, it is imperative to reduce the amount of Pt that they use. Presently, PEFCs use cathodes (the positive electrode) made with Pt nanoparticles (NPs) that are supported on carbon black (PtNPs/CB). However, recent research has indicated that Pt nanoclusters (Pt NCs) have higher oxygen reduction reaction (ORR) activity than Pt NPs, i.e., they have higher performance. Thus far, the reason for Pt NCs high ORR activity has been unclear.

Recently, a research team led by Professor Yuichi Negishi from Tokyo University of Science (TUS) have developed a novel Pt NC that exhibits 2.1 times higher ORR activity than commercial Pt NPs and elucidated the origin of its high activity. “In our study, we focused on Pt NCs derived from a Pt, carbon carboxylate (CO), and triphenylphosphine (PPh3) base i.e., [Pt17(CO)12(PPh3)8]z (where z = 1+ or 2+). We recently showed that these Pt NCs, unlike others, are stable in air. We then performed density functional theory (DFT) calculations to reveal the reason for its remarkable activity,” says Prof. Negishi. The research team also included Junior Associate Professor Tokuhisa Kawawaki from Tokyo University of Science, Associate Professor Kenji Iida from Hokkaido University, Professor Toshihiko Yokoyama from Institute for Molecular Science, Japan, and Professor Gregory F. Metha from the University of Adelaide, Australia. The study has been published in the journal Nanoscale on 24 March 2023.

The researchers prepared the Pt NCs by the adsorption of [Pt17(CO)12(PPh3)8]z onto carbon  black, followed by a calcination reaction. They then compared its performance to conventional Pt
NPs/CB using a technique called linear sweep voltammetry. They found that the novel Pt NCs had higher performance than the Pt NPs/CB. Notably, at 0.9 volts, the Pt NCs had 2.1 times higher activity than the Pt NPs/CB. They also found that increasing Pt loading in the electrode leads to an increase in its mass activity, and that the PT NCs had higher durability than the commercial PT
NPs/CB.

Next, to elucidate the origins of its high activity, they performed DFT calculations. “Our calculations suggest that the high ORR activity of the novel Pt NCs is due to the surface Pt atoms, which have an electronic structure that is suitable for the progress of ORR,” reveals Prof. Negishi.

These findings can serve as a guideline for the design of future high-activity, high-performance Pt catalysts for use in PEFCs, which will take us one step further towards mitigating climate change and the fossil fuel crisis.

Reference

Title of original paper: Pt17 nanocluster
electrocatalysts: preparation and origin of high oxygen reduction reaction
activity

Journal: Nanoscale

DOI: https://doi.org/10.1039/D3NR01152F

Enzymes producing reactive oxygen species may be involved in lignin biosynthesis and growth of coniferous plants

Reactive oxygen species (ROS) are toxic compounds generated by living systems through aerobic respiration and photosynthesis. Now, researchers from Finland and Tokyo University of Science, Japan have studied the mechanism to regulate the activity of ROS-producing enzymes and revealed that ROS is involved in the growth of spruce and synthesis of lignin, a key cell wall component. The findings could help develop technologies for producing valuable timber-based materials and boost the growth of coniferous trees.

Norway spruce is a large coniferous tree native to Northern, Central, and Eastern Europe. Conifers make up a considerable portion of the terrestrial biomass and serve as a significant carbon sink, with the majority of the carbon going into the cell walls of the wood tissues. The economically-important Norway spruce is no exception.

The Norway spruce is a model species of gymnosperm—woody plants that produce naked seeds, on cones, without forming flowers and fruits—whose secondary xylem (water-conducting vascular tissue, also called ‘wood’) cell wall contains 27% of an important phenolic polymer—lignin. Lignin provides rigidity and structural support to cell wall polysaccharides. It is also valued for the production of important bio-based materials. Thus, the Norway spruce holds significance not just as an important lumber crop but also as a source of rich organic chemicals.

As such, much research has been conducted over the years to unravel the intricate metabolic pathways involved in the growth and metabolite production in this species, at the forefront of which are researchers in Finland.

Now, Professor Kazuyuki Kuchitsu at Tokyo University of Science (TUS), Japan, a leading researcher on reactive oxygen species (ROS) in plants has collaborated with Finnish scientists to study lignin biosynthesis in spruce.

Previous research has shown that the last polymerization stages in the production of lignin involve the oxidation of monolignols to phenolic radicals, which are then coupled non-enzymatically, using either hydrogen peroxide (H2O2)-using peroxidase or oxygen-using laccase. With time, the role of ROS biogenic enzymes in lignin synthesis and spruce growth has also been identified.

ROS, such as superoxide anion radicals, H2O2, and hydroxyl radicals, can be produced by a number of sources in the plasma membrane and cell walls of plants and enter the apoplast (the space outside the plasma membrane of a plant cell). These sources include different enzymes, for instance, oxidases and peroxidases, as well as respiratory burst oxidase homologues (RBOHs, also known as NADPH oxidases). Using cytoplasmic NADPH (reduced nicotinamide adenine dinucleotide phosphate) as an electron donor, the plant RBOHs produce superoxide anion radicals, which then dismutate to H2O2. Prof. Kuchitsu’s research has revealed that this mechanism of producing ROS is crucial for many molecular processes in plants including pollen tube growth and fertilization.

In the lignin-forming cell culture and developing xylem of the Norway spruce, PaRBOH1 is the most highly expressed RBOH gene.

But how is PaRBOH1 regulated?

To answer this question, Prof. Kuchitsu’s team from TUS in collaboration with Finnish scientists studied the ROS-producing activity and regulatory mechanism of PaRBOH1 in gymnosperms, including the coniferous species spruce. Their study revealed, for the first time, that PaRBOH1 is activated by calcium ions and phosphorylation to produce ROS. Additionally, protein kinase activity was observed in the cell extract of the developing xylem, phosphorylating certain serine and threonine residues in PaRBOH1.

These findings have been published in volume 13 of Frontiers of Plant Science on 13 October
2022. The multinational team involved in the study included Dr. Kenji Hashimoto from TUS; Dr. Kaloian Nickolov of the University of Oulu, Finland; Dr. Adrien Gauthier of Aghyle Unit, Institut
Polytechnique UniLaSalle, France; and Dr. Anna Kärkönen of the Natural Resources Institute Finland (Luke), Finland.

The results of RBOH regulation in the first gymnosperm species to be examined, the Norway spruce, demonstrates that all seed plants—gymnosperms (naked seeded) or angiosperms (closed seeded)—share the same mechanisms for controlling RBOH activity.

Prof. Kuchitsu explains why this is significant: “ROS were typically regarded as toxic substances, but our study shows that several plant functions, including stress response and plant vegetative
and reproductive development, are regulated by ROS produced by ROS biogenic enzymes.”

Prof. Kuchitsu also sheds light on the practical applications of their findings. Owing to their potential for use as new sources of energy and materials, research into tree development and the
mechanisms governing the valuable components in their cells is gaining momentum. “Our research, in the future, might contribute to the promotion of tree growth and aid in advancing technology for producing valuable materials,” observes Prof. Kuchitsu.

Will the findings contribute to meeting our energy and materials demands while complying with the global sustainable development goals? The researchers are hopeful they will, and so are we.

Reference                     

Title of original paper: Regulation of PaRBOH1-mediated ROS Production in Norway Spruce by Ca2+ Binding and Phosphorylation

Journal: Frontiers in Plant Science

DOI: https://doi.org/10.3389/fpls.2022.978586

Scientists from Japan reveal the crystal structure of a cell cycle motor protein, which could be a potential anticancer drug candidate

Many anticancer drugs have serious side-effects in clinical practice. Kinesin inhibitors block kinesin motor proteins required for cancer cell division, and are thus, promising anticancer drug candidates with minimal side-effects. However, their association with kinesin proteins remains unclear. Researchers from Japan have now addressed this gap by solving the crystal structure of the complex formed by the kinesin protein CENP-E and the non-hydrolyzable ATP analogue AMPPNP, paving the way for the development of cancer therapies with lesser toxicities.

Anticancer drugs are pivotal to cancer treatment, but their toxicity may not always be limited to cancer cells, resulting in harmful side-effects. To develop anticancer therapies that have fewer adverse effects on patients, scientists are now focusing on molecules that are less toxic to cells. One such group of drugs is the “kinesin inhibitors.” These inhibitors prevent cancer progression by explicitly targeting kinesin motor proteins, which are required for the division of cancer cells. Centromere-associated protein E (CENP-E), a member of the kinesin motor protein, is a promising target for inhibitor therapy, as it is essential for tumor cell replication. However, determining the structure of CENP-E is crucial to identify inhibitor molecules that can bind to CENP-E and arrest the function.

Interestingly, the binding of the energy molecule—adenosine triphosphate (ATP)—to the motor domain of CENP-E changes its structure or configuration. This also occurs when CENP-E binds to an inhibitor. So far, very few CENP-E inhibitors have been reported and none have been approved for clinical use. It is, therefore, important to acquire structural information on the CENP-E motor
domain.

To this end, a research team from Tokyo University of Science (TUS) in Japan used X-ray crystallography to elucidate the crystal structure of the complex formed by the CENP-E motor domain and a kinesin inhibitor.

The study, which was led by Professor Hideshi Yokoyama from TUS, along with co-authors Ms. Asuka Shibuya from TUS, and Assistant Professor Naohisa Ogo, Associate Professor Jun-ichi Sawada, and Professor Akira Asai from the University of Shizuoka, was published in FEBS Letters on February 23, 2023. “CENP-E selectively acts on dividing cells, making it a potential new target for anticancer drugs with fewer side-effects”, says Dr. Yokoyama while discussing the motivation underlying this study.

First, the team expressed the CENP-E motor domain in bacterial cells, following which they purified and mixed it with adenylyl-imidodiphosphate (AMPPNP)—a non-hydrolyzable ATP analogue. The mix was crystallized to obtain exhaustive X-ray data. Using this data, the team obtained the structure of CENP-E motor domain-AMPPNP complex. Next, they compared the structure with that of CENP-E-bound adenosine diphosphate (CENP-E-MgADP) as well as with other previously known kinesin motor protein-AMPPNP complexes. From these comparisons, the team speculated that the helix alpha 4 in the motor domain was likely to be responsible for the loose binding of CENP-E to microtubules, i.e., cell structures that are crucial to cell division.

“Compared to the α4 helices of other kinesins, the α4 of CENP-E binds slowly and with lesser strength to microtubules as compared to other kinesins, throughout the ATP hydrolysis cycle”, adds Dr. Yokoyama.

The discovery of the crystal structure of the complex is expected to facilitate additional structure-activity relationship studies, which will bring scientists a step closer to developing anticancer drugs targeting CENP-E. The research team is optimistic about the future applications of their research and are confident that it will be possible to design drugs based on the methods employed in this study. “The ultimate goal is to use the preparation and crystallization methods described in our study for future drug design studies that aim at developing anticancer drugs with fewer side-effects,” concludes a hopeful Dr. Yokoyama.

We, too, believe that this study will bring cancer patients new hope and alleviate the side-effects they experience during treatment.

Reference                     

Title of original paper: Crystal structure of the motor domain of centromere-associated protein E in complex with a non-hydrolysable ATP analogue

Journal: FEBS Letters

DOI: https://doi.org/10.1002/1873-3468.14602

The team led by Tokyo University of Science researchers identified the mechanism using mouse models and validated it with clinical samples

Colorectal cancer is associated with significant mortality. However, the precise mechanism of action that governs the development of colorectal cancer remains largely unknown. A research team led by scientists from the Tokyo University of Science has
recently been able to show that the receptor protein “Dectin-1” promotes colorectal tumorigenesis by enhancing the production of prostaglandin E2, which in turn suppresses the expression of the tumor-inhibitory IL-22-binding protein.  

Colorectal cancer (CRC) causes nearly 500,000 deaths every year across the globe. Although
CRC is predominantly associated with old age and poor dietary habits, the precise pathophysiological mechanisms that contribute to the development of CRC continue to remain elusive. Now, a research team—led by Professor Yoichir Iwakura from Tokyo University of Science, Japan, and Professor Ce Tang from Sun Yat-sen University China—has recently been able to identify the underlying mechanism using a mouse model and clinical samples. Their results have been published in Nature Communications. This paper was published online in Volume 14 Issue 1 of the journal on March 17, 2023. 

“We investigated the role of Dectin-1 in colorectal tumorigenesis by analyzing mouse intestinal tumor models and clinical samples from patients with CRC. We showed that Dectin-1 signaling promotes the development of colorectal tumors by enhancing the production of prostaglandin E2 (PGE₂), which facilitates CRC development by suppressing the expression of the tumor-inhibitory IL-22-binding protein (IL-22BP),” says Prof. Iwakura.

Dectin-1 primarily serves as a receptor protein and preferentially binds to β-glucans—glucose
polymers that naturally occur in the cell walls of various types of fungi. Although prior studies have shown that Dectin-1 offers protection against fungal invasion, the current study highlights its role as a receptor protein involved in the development of CRC.

To fully understand the underlying mechanism of Dectin-1’s pathophysiological action in
CRC, the research team generated genetically modified “Clec7a^–/– mice” that were deficient in Dectin-1. For this purpose, the team used the Apc^Min mouse model of human familial adenomatous polyposis a form of cancer characterized by multiple tumors—as well as the azoxymethane (AOM)-dextran sodium sulfate (DSS)-induced colorectal cancer model of chemical carcinogenesis. Quite interestingly, Clec7a^–/– mice showed reduced tumorigenesis in both of the above models, thus underscoring the role of Dectin-1 in CRC development. 

Next, the researchers decided to investigate the role of gut bacteria in intestinal tumorigenesis. To this end, they created germ-free (GF) mice that harbored no commensal bacteria in their guts. They found that, in the complete absence of any gut bacteria, colorectal polyp number in Clec7a^−/− GF mice was greatly reduced compaired with wild type GF mice, showing that gut microbiota are not involved in the reduction of polyps in Clec7a^–/– mice.                

The team then decided to delve into the associated mechanism of action. Subsequent murine-model-based experiments revealed that PGE₂ levels in tumors were reduced in Clec7a^−/−
mice. Moreover, they also observed a reduction in the expression of PGE₂ synthases such as COX2 which is known to promote intestinal tumorigenesis.  

Furthermore, while investigating the types of cells that produced PGE₂ synthases, the researchers
found that it is mainly produced by myeloid cell-derived suppressor cells (MDSCs) that have infiltrated into the colorectal tumor. In addition, the researchers also demonstrated that PGE₂ promoted the differentiation and proliferation of MDSCs, further contributing to the development of CRC in the murine models.

While attempting to elucidate the underlying mechanism of action, the researchers also noticed that Clec7a^−/− mice showed an increased production of IL-22BP—a protein that can suppress the development of colorectal tumors by binding and inhibiting the pro-inflammatory protein Interleukin-22 (IL-22). Deletion of the gene responsible for the expression of IL-22BP caused
increased polyps and early death in Apc^Min mice, thus underscoring the role of IL-22BP in tumor suppression. Moreover, the production of IL-22BP was found to be strongly suppressed by PGE₂.

Interestingly, laminarin, a low-molecular-weight β-glucan from seaweeds, significantly inhibited AOM-DSS-induced colonic tumorigenesis in mice that were fed with this compound. The team also found that whereas high-molecular-weight β-glucans promoted tumor growth, low-molecular-weight β-glucans suppressed it, by suppressing Dectin-1 signaling.

These results also have immediate clinical implications. For instance, the team noticed that patients with CRC showing low CLEC7A expression survived longer than those with high expression of CLEC7A (in the MDSCs). Moreover, in patients with CRC, IL22RA2 expression was decreased and that of PTGS2—a PGE₂-synthesizing enzyme—was increased in tumors compared to in normal tissues.       

Prof. Iwakura concludes, “Dectin-1 plays a key role in the development of colorectal tumorigenesis in both mice and humans, through the modification of PGE₂ and IL-22BP levels. Dectin-1, therefore, serves as an attractive target for the development of novel anti-CRC therapeutics.” 

These findings are groundbreaking and make a significant contribution toward our present understanding of the genesis of colorectal cancer. Further research along this direction will be sure to aid in the prevention and treatment of this high-mortality disease. 

Reference                      

Title of original paper: Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression

Journal:  Nature Communications

DOI:https://doi.org/10.1038/s41467-023-37229-x

 

Researchers from Tokyo identified a natural immunomodulator, β-damascone, and explored its molecular function in detail.

Dendritic cells (DCs) perform several important immunological functions. However, their hyperactivity can result in inflammatory and autoimmune diseases. Now, to identify natural compounds that can regulate DC-mediated functions, a group of researchers screened 150 natural aroma compounds. They discovered that β-damascone, a major aroma component of rose, can suppress DC-mediated immune functions. In vivo experiments in mice models demonstrated that β-damascone has anti-inflammatory properties and can be promising as an effective immunomodulatory drug.

Dendritic cells (DCs) are important players of the immune system with important functions such as the identification of infectious pathogens, production of cytokines (chemical signalers of the immune system), presentation of antigens to activate T-cells, and more. Despite performing such key functions, DCs may lead to inflammatory and autoimmune diseases when hyperactive. Therefore, to prevent DC-mediated diseases, it is necessary to identify molecules that can modulate the functions of DCs.

Previous studies have indicated that natural compounds can serve as potent immunomodulators. To explore the role of such compounds in modulating the functions of DCs, a team of researchers from Japan, led by Prof. Chiharu Nishiyama from Tokyo University of Science, including Dr. Hikaru Okada, Dr. Masakazu Hachisu, and Dr. Naoki Kodama screened 150 types of natural aroma compounds. “Natural fragrant compounds are found in plants and microorganisms and are also commonly used in foods and daily necessities. However, not much research has been conducted on the physiological activities of individual flavor compounds, particularly on immune responses,” remarks Prof. Nishiyama while discussing their motivation behind this study, which was published in Frontiers in Nutrition on February 9, 2023.

First, the team conducted a two-step screening process of aroma compounds, which led to the identification of a novel and effective modulator of DCs known as β-damascone—a primary component that constitutes rose fragrance.

Next, through a series of molecular and immunological assays, the team found out that β-damascone inhibited several functions of DCs including antigen-dependent activation of CD4+ T-cells and the development of Th1 cells (Type-1 helper cells). In addition, β-damascone reduced the production of inflammatory cytokines such as, interleukin (IL)-6,
IL-12p40, and tumor necrosis factor (TNF)-a.

Discussing these findings, Prof. Nishiyama further adds, “We wanted not only to observe the effective active ingredients, but also to thoroughly examine their mechanisms of action at the molecular level, up to the point of verifying whether they exert physiologically meaningful effects.” True to their word, on exploring the mechanisms underlying the inhibitory functions of β-damascone, the team noted that these functions were mediated by NRF2—a master transcription factor with crucial antioxidative roles. NRF2 was found to exert these effects via its target genes, Hmox1 and Nqo1.

The function of β-damascone was further confirmed by in vivo experiments in contact hypersensitivity mice models. The oral administration of β-damascone reduced ear inflammation in these mice models. Notably, these experiments also corroborated the role of NRF2 in β-damascone-mediated immunomodulation. Indeed, ear swelling was not suppressed in NRF2 knockout mice models, i.e., mice that lacked NRF2.

Taken together, this comprehensive study showed that β-damascone can function as an efficient modulator of DC-mediated functions and can effectively reduce the inflammatory effects of DC-hyperactivation.

We are confident that these findings will lead to the application of β-damascone as a safe and effective immunomodulatory drug very soon!

The proposed method produces wiring suitable for developing all-carbon devices, including flexible sensors and energy conversion and storage devices

Researchers from Tokyo University of Science in Japan have developed an inexpensive method for fabricating multi-walled carbon nanotubes (MWNTs) on a plastic film. The proposed method is simple, can be applied under ambient conditions, reuses MWNTs, and produces flexible wires of tunable resistances without requiring additional steps. It eliminates several drawbacks of current fabrication methods, making it useful for large-scale manufacturing of carbon wiring for flexible all-carbon devices.

Carbon nanotubes (CNTs) are cylindrical tube-like structures made of carbon atoms that display highly desirable physical properties like high strength, low weight, and excellent thermal and electrical conductivities. This makes them ideal materials for various applications, including reinforcement materials, energy storage and conversion devices, and electronics. Despite such immense potential, however, there have been challenges in commercializing CNTs, such as their incorporation on plastic substrates for fabricating flexible CNT-based devices. Traditional fabrication methods require carefully controlled environments such as high temperatures and a clean room. Further, they require repeat transfers to produce CNTs with different resistance values.

More direct methods such as laser-induced forward transfer (LIFT) and thermal fusion (TF) have been developed as alternatives. In the LIFT method, a laser is used to directly transfer CNTs
onto substrates, while in TF, CNTs are mixed with polymers that are then selectively removed by a laser to form CNT wires with varying resistance values. However, both these methods are expensive and have their unique problems. LIFT requires expensive pulsed lasers and preparation of CNTs with specific resistance values, while TF uses large amounts of CNTs that are not
utilized and go to waste.

Aiming to develop a more simple and inexpensive approach, Associate Professor Dr. Takashi Ikuno along with his collaborators, Mr. Hiroaki Komatsu, Mr. Yosuke Sugita and Mr. Takahiro Matsunami at Tokyo University of Science, Japan, recently proposed a novel method that enables fabrication of multi-walled CNT (MWNT) wiring on a plastic film under ambient conditions (room temperature and atmospheric pressure) using a low-cost laser.

The breakthrough, published in the journal Scientific Reports on 08 February 2023, involves coating a polypropylene (PP) film with an MWNT film about 10 μm thick and then exposing it to a mW UV laser. The result is a conductive wiring made of a combination of MWNT and PP.

“This process enables the easy ‘drawing’ of wiring and flexible devices for wearable sensors without the need for complex processes,” highlights Dr. Ikuno.

The researchers attributed the formation of these wires to the difference in the thermal conductivities between the MWNT and the PP film. As the MWNT/PP film is exposed to the laser, the high thermal conductivity of the MWNT layer causes the heat to spread along the length of the wire, resulting in high temperatures at the MWNT–PP interface and lower temperatures elsewhere in the PP film. Directly below the laser, where temperatures are the highest, the PP diffuses into the MWNT film to form a thick PP/MWNT composite, while a thin PP/MWNT layer is formed at the edges of the laser where temperatures are relatively low.

The proposed method also allows the fabrication of carbon wires with different resistance values within the same process (without repeat transfer) by simply changing the irradiation conditions, thereby eliminating the need for additional steps. Exposing the PP/MWNT film to high laser energies, achieved either by low scanning speeds, a high number of laser exposures, or the use of a high-powered laser, produces thicker wires with a higher concentration of MWNTs. Consequently, the lower resistivity of MWNT and the thicker wire lowers the resistance per unit length of the wire (resistance is directly proportional to the ratio between the resistivity and the thickness of the wire).

By precisely controlling the exposure of the MWNT/PP film to laser light, the researchers successfully fabricated MWNT wires with a wide range of resistance values, from 0.789 kΩ/cm to 114 kΩ/cm. Moreover, these wires were highly flexible and maintained their resistance even when bent repeatedly.

Additionally, the method solved one of the pressing issues with current techniques, namely the inability of LIFT and TF techniques to reuse CNTs not utilized in the fabrication process. In the proposed method, MWNTs not incorporated into the PP film during laser irradiation can be recovered and reused, allowing for the creation of new MWNT wires with little to no change in resistance values.

With its simplicity, efficient utilization of CNTs, and the capability to create high-quality wires, the new method has the potential to realize large-scale manufacturing of flexible carbon wiring for flexible sensors and energy conversion and storage devices.

“We expect the process cost to be significantly reduced compared to that for conventional methods. This, in turn, will contribute to the realization of low-cost flexible sensors that are expected to have wide applications in large quantities,” concludes Dr. Ikuno.

***

Reference

Title of original paper: Direct formation of carbon nanotube wiring with controlled electrical resistance on plastic films

Journal: Scientific Reports

DOI: https://doi.org/10.1038/s41598-023-29578-w

Spin, a quantum property of particles, can be controlled using light waves to store information.

This is conventionally achieved using a uniformly polarized light beam. Recently, researchers from Japan successfully generated a structured light beam with spatially variant polarization and transferred its structure to electron spins confined within a semiconductor solid. Additionally, they simultaneously generated two spin waves with inverted phases using this beam. Their results have important implications in optical communications and information storage.

Light is composed of electric and magnetic fields that oscillate perpendicular to each other. When these oscillations are restricted, say, along a plane, it results in polarized light. Polarized light is of great importance in optical communications and can similarly revolutionize how information is stored.

Current electronic devices store information in the form of electronic charge. However, spin – a uniquely quantum property of electrons – offers an alternative. The spin can be controlled using polarized light to store information. A polarized light beam interacts with electron spins within a semiconductor to generate spin-polarized electrons, i.e., spins aligned along a specific direction. So far, only uniformly polarized light, i.e., light with a spatially uniform polarization, has been exploited to control electron spins. If, however, the polarization has an additional spatial structure (variation), it can produce spatially structured electron spins, opening up new ways to store information.

To this end, a group of researchers, led by Junior Associate Professor Jun Ishihara from and including Graduate Student Takachika Mori, Graduate Student (at the time of the research) Takuya Suzuki, and Professor Kensuke Miyajima from Tokyo University of Science (TUS), Japan, has now devised a method for generating such spatially structured electron spins using a structured light with spatially varying polarization profile. The study, published in the journal Physical Review Letters, was done in collaboration with research groups from Chiba University, Tohoku University, and Tsukuba University in Japan.

“In this work, we generated a doughnut-shaped structured light–a vector optical vortex beam with an orbital angular momentum (OAM)– from a basic Gaussian beam using vortex half-wave plate and quarter-wave plate devices. We then used this beam to excite the electron spins confined within a gallium arsenide/aluminum gallium arsenide semiconductor quantum well. These spins, in turn, formed a helical spatial structure in a circle,” explains Dr. Ishihara.

Interestingly, while the beam with an OAM number equal to one produced a helix with two spin periods – spin up and spin down – around the circle, an OAM number of two resulted in a helix with four such alterations. These observations indicated that the spatial polarization structure of the optical vortex, determined by the OAM, was transferred to the electron spins inside the semiconductor. In addition, increasing the OAM number was suggested to enable higher information storage capacity, characterized by higher spin repetition rate around the circle.

Moreover, the researchers utilized the effective magnetic field of the spin-orbit interaction acting on electron spins in the quantum well to simultaneously generate two spin waves with opposite phases in the vertical direction using a single beam. This suggested that various spin states with spatial structures could be produced by exploiting the effective magnetic fields (a characteristic of solids) alongside structured light beams.

With such exciting results, the researchers discuss the future prospects of their work. “The conversion of the spatial polarization structure of light into a spatial structure of spin along with the generation of new spin spatial structures in combination with effective magnetic fields in solids are expected to lead to elemental technologies for higher-order quantum media conversion and information capacity enhancement using spin textures,” says Dr. Ishihara.

It may not be long before such spin-based information storage devices become a reality!***

Reference:

Title of original paper: Imprinting spatial helicity structure of vector vortex beam on spin texture in semiconductors

Journal: Physical Review Letters

DOI: https://doi.org/10.1103/PhysRevLett.130.126701

Researchers achieve carrier modulation and improved switching response speed control in these batteries

Development of all-solid-state batteries is crucial to achieve carbon neutrality. However, their high surface resistance causes these batteries to have low output, limiting their applications. To this end, researchers have employed a novel technique to investigate and modulate electric double layer dynamics at the solid/solid electrolyte interface. The researchers demonstrate unprecedented control of response speed by over two orders of magnitude, a major steppingstone towards realization of commercial all-solid-state batteries.

In our quest for clean energy and carbon neutrality, all-solid-state lithium-ion batteries (ASS-LIBs) offer considerable promise. ASS-LIBs are expected to be used in a wide range of applications including electric vehicles (EVs). However, commercial application of these batteries is currently facing a bottleneck—their output is reduced owing to their high surface resistance. Moreover, the exact mechanism of this surface resistance is hitherto unknown. Researchers have alluded it to a phenomenon called the “electric double layer” (or EDL) effect seen in colloidal substances (which are microscopic dispersions of one kind of particle in another substance). The EDL effect occurs when colloidal particles gain negative electric charge by adsorbing the negatively charged ions of the dispersion medium on their surface. “This occurs at the solid/solid electrolyte interface, posing a problem in all-solid-state lithium batteries,” explains Dr. Tohru Higuchi, Associate Professor at Tokyo University of Science (TUS). Dr. Higuchi, along with colleagues Dr. Makoto Takayanagi from TUS, and Dr. Takashi Tsuchiya and Dr. Kazuya Terabe from National Institute for Materials Science in Japan, has devised a novel technique to quantitatively evaluate the EDL effect at the solid/solid electrolyte interface.

An article detailing their technique was made available online on 8 February 2023 and was published in Volume 31 of Materials Today Physics. The researchers employed an all-solid-state hydrogen-terminated diamond (H-diamond)-based EDL transistor (EDLT) to conduct Hall measurements and pulse response measurements that determined EDL charging characteristics. By inserting a nanometer-thick lithium niobate or lithium phosphate interlayer between the H-diamond and lithium solid electrolyte, the team could investigate the electrical response of the EDL effect at the interface between these two layers. The electrolyte’s composition did, indeed, influence the EDL effect in a small region around the electrode interface. The EDL effect was reduced when a certain electrolyte was introduced as an interlayer between the electrode/solid electrolyte interface. EDL capacitance for the lithium phosphate/H-diamond interface was much higher compared to the lithium niobate/H-diamond interface.

Their article also explains how they improved the switching response time for charging ASS-EDLs. “The EDL has been shown to influence switching properties, so we considered that the switching response time for charging ASS-EDLs could be greatly improved by controlling the capacitance of the EDL. We used the non-ion-permeable property of diamond in the electron layer of the field-effect transistor and combined it with various lithium conductors,” Dr. Higuchi narrates.

The interlayer accelerated and decelerated the EDL charging speed. The electrical response time of the EDLT was highly variable—it ranged from about 60 milliseconds (low speed switching for lithium phosphate/H-diamond interface) to about 230 microseconds (high speed switching for lithium niobate/H-diamond interface). The team, however, exhibited control over the EDL charging speed for over two orders of magnitude.

In summary, the researchers were able to achieve carrier modulation in all-solid-state devices and improved their charging characteristics. “These results from our research on the lithium-ion conductive layer are important for improving the interface resistance and may lead to the realization of all solid-state batteries with excellent charge-discharge characteristics in the future”, notes an optimistic Dr. Higuchi.

Taken together, this is a major stepping stone towards controlling the interface resistance of ASS-LIBs that catalyzes their feasibility for many applications. It will also help design better solid-electrolyte-based devices, a class of gadgets which also includes neuromorphic devices.