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Tag: Japan

New treatment for inflammatory bowel disease

Posted on by Tokyo University of Science

In a recent study published in Frontiers in Immunology, Prof. Chiharu Nishiyama, Kazuki Nagata, and Ayumi Okuzumi from the Tokyo University of Science and Prof. Hiroshi Nagase from the University of Tsukuba attempted to understand the effects of opioids on the immune system. They tested the effects of KNT-127—an artificially synthesized opioid that activates delta-opioid receptors—on immune responses in live animal and cell culture experiments.

When mice with inflammatory bowel disease (IBD) were treated with KNT-127, they showed a reduction in the severity of colitis—a form of colon inflammation—indicated by lower weight loss and colon atrophy and improved disease activity scores. Similar results were also obtained in a recovery model, confirming the beneficial effects of KNT-127 against colonic inflammation.

Although these results were promising, an important caveat still loomed. “Before proceeding with additional experiments, we had to rule out the role of CNS opioid receptors in the anti-inflammatory effects of KNT-127,” says Prof. Nishiyama, the lead researcher on the study.

To address this, the researchers performed similar experiments with YNT-2715, a peripheral KNT-127 that cannot cross over from the blood to the brain. The results were similar to those observed with KNT-127, confirming that its anti-inflammatory effects were indeed CNS-independent.

Encouraged by this, the group examined other immune-related effects of KNT-127 treatment in the colitis model. They found that during disease progression, the opioid reduced the serum levels of IL-6, a pro-inflammatory factor, while also decreasing the number of macrophages in the mesenteric lymph nodes (MLNs).

Interestingly, they also observed an increase in the number of regulatory T cells (Tregs) in MLNs. Together, their results showed that KNT-127 suppresses the inflammation caused by macrophages during disease progression and enhances the anti-inflammatory response due to Tregs during recovery.

Finally, to understand the direct effects of KNT-127 on immune cells, the researchers performed in vitro experiments in which they treated macrophages derived from bone marrow or T cells from the spleen with the drug. The results were consistent with those from animal experiments, revealing increased secretion of the pro-inflammatory signals as well as enhanced development of Tregs in response to KNT-127 treatment.

Altogether, the findings demonstrated that KNT-127 can directly act on immune cells and reduce the severity of inflammation, making it a good candidate for the treatment of IBD.

“Several people around the world suffer from diseases related to colon inflammation, and so far, optimal treatment strategies are lacking. Our findings show that KNT-127 and other activators of opioid receptors could be promising therapeutic options for such diseases,” comments Prof. Nagase, the chief drug developer behind the synthetic opioid, while also cautioning of the road ahead.

“Of course, before these drugs are used clinically, additional experiments will be required to elucidate how they exert their immunomodulatory functions and what their effects on other immune diseases are,” he adds.

Nevertheless, Prof. Nishiyama and her team are confident that their study represents an important milestone, not only towards the treatment of IBD but also towards our understanding of the “brain-gut axis”—the interrelationship between brain and gut function—which has received increasing attention in recent years.

“Today, we know that poor mental health has physical manifestations. For example, stress worsens inflammation in the gut, which in turn affects the health of the brain. Our results on the immune-related effects of opioids, which commonly act on the brain, is a step toward unravelling the biological mechanisms that govern the reciprocative relationship of gut health and the immune system with the CNS,” mentions Prof. Nishiyama, excited about what the future holds.

Hidden in the Seeds: Bacteria found to survive the harsh interior of Passion Fruit seeds

Posted on by Tokyo University of Science

For the first time ever, a research group consisting of Dr. Toshiki Furuya, Associate Professor at the Department of Applied Biological Science, Tokyo University of Science, Japan, has succeeded in isolating bacteria from the seeds of passion fruit (Passiflora edulis). Their research, which also unearths the surviving mechanisms of these bacteria inside the seeds, has been published in the journal MicrobiologyOpen.

In their study, the scientists focused on the seeds of P. edulis. The seeds of this fruit are full of secondary metabolites with strong antimicrobial properties, such as resveratrol and piceatannol—the latter present at high levels of up to 2.2 mg/g.

As Dr. Furuya reveals the rationale behind choosing passion fruit seeds for the study, “The extraordinarily high concentration of piceatannol protects P. edulis seeds from microorganisms. We thought it would be interesting to know if any endophytic microorganism could survive this extreme environment and if yes, how.”

Earlier reports showed that endophytes capable of surviving in an environment rich in biologically active compounds possessed biocatalytic activities related to the metabolism of these compounds. The fact that their biocatalytic potential could be exploited for therapeutic purposes made the scientists even more eager to explore the presence of endophytic bacteria.

The scientists collected and surface-sterilized the seeds of naturally grown P. edulis before either cutting or crushing them and placing them on solid agar-based growth media to check for microbial growth. While no microbial colony appeared from the cut or homogenized seeds, interestingly, the seedlings sprouting from the cut seeds, when exposed to growth media, gave rise to microbial colonies. The scientists then performed sequencing to identify the bacteria that appeared on the agar plate.

The findings were remarkable. From the seedlings, the scientists isolated 19 strains, including three previously unreported strains of bacteria from various genera. They hypothesized that inside the seeds, piceatannol exerted bacteriostatic (or “bacterial growth-stalling”) rather than bactericidal (or “bacteria-killing”) effects on the residing bacteria.

Ms. Aoi Ishida, the co-author of the study explains: “Due to the presence of a high concentration of piceatannol, the growth of the bacteria was stagnated inside the seed, but when transmitted to the next-generation seedlings during germination, the bacteria were relieved from the effect of piceatannol and able to grow again.”

The scientists also found one of the bacteria, Brevibacterium sp. PE28-2, to possess the ability to convert resveratrol and piceatannol to their respective derivatives. This is the first endophyte shown to exhibit such activity.

Dr. Furuya and Ms. Ishida are very hopeful that the method established in this study is expected to be effective in isolating several useful endophytic bacteria from a variety of plants. Moreover, considering the current focus on engineering new biomolecules with diverse applications, the results of this study would accelerate research on seed endophytic bacteria.

“Second-Hand” psychological stress can lead to depression in mice, finds study

Posted on by Tokyo University of Science

In a pioneering study, scientists from Japan established that psychological stress can negatively affect neurogenesis and cause depression in a mouse model.

Recent research has explained how vicarious social defeat can cause psychological stress in mice. This involves the mouse being made to experience the defeat of another mouse in an experimental social setting. Using this model, a group of scientists from Japan attempted to establish a link between depressive symptoms and hippocampal neurogenesis.

Professor Akiyoshi Saitoh from Tokyo University of Science, one of the lead authors of the study, further explains the motivation behind this research, “The number of individuals suffering from depression has been on the rise the world over. However, the detailed pathophysiology of depression still remains to be elucidated. So, we decided to focus on the possible mechanism of psychological stress in adult hippocampal neurogenesis, to understand its role in depressive disorders.” The study was published in the journal Behavioural Brain Research.

After exposing the mice to chronic vicarious social defeat stress, Prof. Saitoh and the team, including Mr Toshinori Yoshioka and Dr Daisuke Yamada from Tokyo University of Science, analyzed their behaviour and brains in close detail.

Aside from behavioural deficits like social withdrawal, the stressed mice also showed a significant decrease in the survival rate of newborn neurons in the dentate gyrus, a region in the hippocampus responsible for sensory perception and memory, compared to the non-stressed controls. This condition persisted for up to four weeks, after “stressing” the mice. However, cell growth, differentiation, and maturation did not differ between the groups of mice during the period of observation. Notably, the cell survival rate was restored in the stressed mice after treatment with a chronic antidepressant called fluoxetine.

Regarding the results, Mr. Toshinori Yoshioka adds, “We have found out that chronic mental stress affects the neurogenesis of the hippocampal dentate gyrus. Also, we believe that this animal model will play an important role in elucidating the pathophysiology of depression, and in the development of the corresponding novel drug.”

Overall, this study has provided important insights into the pathophysiology of depression. Also, it goes without saying how this study paves the way for future research into the role of psychological stress in depression.

Scientists unravel the mysteries of irreversibility in electrochromic thin films

Posted on by Tokyo University of Science

Scientists from Japan have quantitatively evaluated ion-trapping-induced degradation in lithium intercalated tungsten oxide films

In a recent study published in Applied Surface Science (made available online on August 13 2021, and to be published in Volume 568 of the journal on December 1 2021), scientists from the Tokyo University of Science and the National Institute for Materials Science (NIMS), Japan, collaborated to quantitatively assess the irreversibility of LixWO3 thin films.

Discussing the key concerns that the study addresses, Associate Professor Tohru Higuchi from Tokyo University of Science, who led the study, observes “There are two critical questions that arise: First, is irreversible Li2WO4 formation different from irreversible Li+ trapping? Second, can these irreversible components coexist?”

He adds, “Conventional measures are unable to differentiate between the two irreversible components. As a result, we conducted a quantitative examination to offer solid answers to these questions.”

The scientists devised a quantitative evaluation method that combines in situ hard X-ray photoelectron spectroscopy (HAXPES) and electrochemical measurements. HAXPES is used to investigate buried interfaces, whereas electrochemical tests are used to examine corrosion properties. The intercalation of Li+ results in a redox reaction that changes the oxidation state of tungsten (W) ions from W6+ to W5+.

Based on this change, HAXPES can evaluate “reversible Li+” and “irreversible Li+ trapping.” However, evaluating “irreversible Li2WO4 formation” using HAXPES is challenging.

Dr Takashi Tsuchiya, a Principal Researcher at NIMS and co-author of the study, explains why: “W ions in Li2WO4 have a stable oxidation state because they exist in the W6+ form. As a result, HAXPES is unable to evaluate the irreversibility caused by Li2WO4 formation. Electrochemical measurements, on the contrary, can distinguish ‘reversible Li+’ from the two irreversible components. Therefore, integrating both methods enables the distinction and quantitative evaluation of all three components.”

To conduct the electrochemical measurements, the scientists built a LixWO3-based redox transistor on the flat surface of a lithium-ion conducting glass ceramic (LICGC). They also built an electrochemical cell with a WO3 thin film as the semiconductor and a LICGC substrate as the electrolyte to conduct HAXPES measurements.

Furthermore, they employed in situ Raman spectroscopy to assess the influence of Li+ insertion on the LixWO3 structure. They were able to successfully determine the increase in crystallinity caused by Li+ insertion. The proportions of reversible Li+, irreversible Li2WO4 formation, and irreversible Li+ trapping were calculated to be 41.4%, 50.9%, and 7.7%, respectively.

The scientists believe that their study will help develop and design improved EC materials and devices.

“For several years, the main impetus for EC research and development has been potential applications in energy-efficient buildings and aircraft. However, there are several other applications as well, such as the energy-saving and vision-friendly electronic paper displays,” says Dr Kazuya Terabe, Principal Investigator of the International Center for Materials Nanoarchitectonics at NIMS and a co-author of the study.

“Moreover, our findings broaden the application possibilities by providing the basis for the future development of high-performance WO3-based EC devices.”

Untangling the irreversibility conundrum is certainly a big step forward, but there is still much work to be done, although the pace is sure to go up.

Self-powered diaper sensors that monitor urine sugar levels

Posted on by Tokyo University of Science

Monitoring urine sugar levels is important during the early stages of diabetes, and diaper sensors represent an attractive solution. In a recent study published in ACS Sensors, Associate Professor Isao Shitanda, Professor Masayuku Itagaki, and Mr Yuki Fujimura from Tokyo University of Science (TUS), Japan, present a promising approach to realizing self-powered diaper sensors that can generate energy directly from urine.

This work was done in collaboration with Associate Professor Seiya Tsujimura from the University of Tsukuba, Japan. Worth noting, this work is in line with other research efforts of Dr. Shitanda and his colleagues to develop self-powered biosensors like a lactate sensor energized entirely by sweat.

The scientists developed a paper-based biofuel cell that, through a pair of reduction-oxidation reactions, outputs electrical power proportional to the amount of glucose in the urine. Important considerations in the design of such biofuel cells are the amount of urine needed to generate enough power and the overall stability and durability of the device.

With this in mind, the scientists developed a special anode, the negative terminal of an electrochemical cell, using a process known as “graft polymerization” that allowed them to firmly anchor glucose-reactive enzymes and mediator molecules to a porous carbon layer, which served as the base conductive material.

The scientists tested their self-powered biosensor in diapers using artificial urine at various glucose concentrations. They used the generated energy to power up a Bluetooth Low Energy transmitter, and remotely monitored the measured concentration using a smartphone. They found that the biofuel cell could detect urine sugar in a very short time (within 1 second).

“Besides monitoring glucose in the context of diabetes, diaper sensors can be used to remotely check for the presence of urine if you stock up on sugar as fuel in advance. In hospitals or nursing care sites, where potentially hundreds of diapers have to be checked periodically, the proposed device could take a great weight off the shoulders of caregivers,” comments Dr Shitanda.

In short, the sensor that Dr Shitanda’s team has engineered can not only prevent diabetes but also make diaper management more efficient and responsive without compromising the environment. “We believe the concept developed in this study could become a very promising tool towards the general development of self-powered wearable biosensors,” says Dr Shitanda.

Is mimamoru, Japan’s hands-off approach in disciplining schoolchildren, worth a try?

Posted on by Hiroshima University

A study examining Japanese schools’ hands-off approach when children fight showed it could create opportunities for autonomy and encourage ownership of solutions, suggesting a new strategy in handling kids squabbles in other countries.

Called mimamoru, the pedagogical strategy is a portmanteau of the Japanese words mi, meaning watch, and mamoru, meaning protect. It’s generally understood as “teaching by watching” — where adults intentionally let kids handle disagreements by themselves to promote learning through voluntary exploration and actions.

“This study aims to understand the reason why Japanese early childhood educators tend not to intervene, and how and in what contexts they do,” said study author and Hiroshima University Associate Professor Fuminori Nakatsubo.

A total of 34 Japanese and 12 US early childhood educators participated in focus groups that used modified video-cued multi-vocal ethnography methods to scrutinize the non-intervention strategy. Their findings are published in the Early Childhood Education Journal.

The study noted that allowing children to experience feelings of physical pain or guilt can be a teachable moment that physical fights do not solve any problem.

The researchers, however, clarified that “watching” doesn’t mean that adults ignore children’s safety. Japanese educators intervene when the risk of physical harm caused by fighting outweighs the benefit for children to learn. This story was first published on the Hiroshima University website.

Researchers determine the mechanisms of ion diffusion in phosphate glass 

Posted on by NITech

Phosphate glasses are expected to have applications in a variety of fields. To improve their functionality, it is necessary to determine the association between their structure and ion diffusion characteristics. Recently, using first-principles molecular dynamic simulations, researchers from Nagoya Institute of Technology, Japan, have provided novel insights into the ion diffusion mechanisms of phosphate glass, suggesting that ionic conductivity and glass solubility can be manipulated by controlling the morphology of the material.

Recently, a team of researchers from Nagoya Institute of Technology, Japan, led by Dr. Tomoyuki Tamura, has theoretically deciphered the ion diffusion mechanism involved in the hydration reaction process of phosphate glasses. Their study has been published in the Physical Chemistry Chemical Physics journal.

In fully connected P2O5-based phosphate glass, three of the oxygen atoms in each phosphate unit are bonded to neighboring phosphorous atoms. To study the dynamics of ions in the phosphate glass during the hydration process, the researchers used a model made of phosphates with QP2 and QP3 morphologies, that contain two and three bridging oxygens per PO4 tetrahedron, respectively, along with six coordinated silicon structures.

The researchers implemented a theoretical computational approach known as “first-principles molecular dynamic (MD) simulation” to investigate the diffusion of proton and sodium ions into the glass.

Explaining the rationale for their unconventional approach, Dr. Tamura says, “First-principles MD simulation enabled us to assume the initial stage of water infiltrating and diffusing into silicophosphate glass and elucidate the diffusion of protons and inorganic ions for the first time.”

Based on their observation, the researchers proposed a mechanism where the protons “hop” and are adsorbed onto the non-bridging oxygen or “dangling” oxygen atom of nearby phosphates through hydrogen bonds. However, in the phosphate glass model they used, the QP2 phosphate units contributed more strongly to the diffusion of protons than the QP3 phosphate units. Thus, they found that the morphology of the phosphate network structure, or the “skeleton” of the glass, greatly affects the diffusion of ions.

They also noticed that when a sodium ion was present in the vicinity, the adsorption of a proton onto a QP2 phosphate unit weakened the electrostatic interaction between sodium and oxygen ions, inducing the chain diffusion of sodium ions.

The demand for new biomaterials for effective prevention and treatment is on the rise, and phosphate glasses are well-poised to fulfil this growing need. A large proportion of the population, comprising both elderly and younger people, suffers from diseases related to bone and muscle weaknesses.

As Dr. Tamura surmises, “Water-soluble silicophosphate glass is a promising candidate for supplying drugs or inorganic ions that promote tissue regeneration, and our study takes the research in glass technology one step nearer towards realizing the goal.”

Researchers design high-activity catalysts from gold nanoclusters

Posted on by Tokyo University of Science

Precise metal nanoclusters (NCs) are ideal for developing practical catalysts for chemical reactions. However, their catalytic activity is reduced either due to protective molecules called “ligands” surrounding them or aggregation resulting from ligand removal. In a new study, scientists from Japan elucidate the ligand removal mechanism for gold NCs and irradiate them with UV light to prevent aggregation, creating a high-functioning photocatalyst.

“When the ligands are removed without special treatment, the metal NCs easily aggregate on the support and lose their size-specific properties. It is essential understand the mechanism of ligand calcination to create highly functional heterogeneous catalysts under appropriate conditions,” says Prof. Yuichi Negishi of Tokyo University of Science, Japan, who researches on the synthesis of
nanoclusters.

In a new study published in Angewandte Chemie, Prof. Negishi led a team of researchers, including Assistant Professor Tokuhisa Kawawaki, Mr Yuki Kataoka, Ms Momoko Hirata, and Mr Yuki Akinaga, to dig deep into the mechanism of the ligand removal process in NCs. For their experiments, the researchers synthesized gold NCs protected by two ligands, 2-phenylethanethiolate and mercaptobenzoic acid and then supported them on a photocatalytic metal oxide.

Next, the team heated the prepared material at different temperatures ranging from 195°C to 500°C. After every step, they analyzed the products using techniques such as infrared spectroscopy, x-ray photoelectron spectroscopy, and transmission electron microscopy to identify the changes in their chemical composition.

After the ligands were completely released, the team embedded the gold NCs within a thin film of chromium oxide by irradiating the sample with UV light in order to prevent aggregation of the NCs. This process generated a photocatalyst with useful properties like high water-splitting activity and stability.

These findings guide the design for metal NC-based catalysts in the future, with applications in hydrogen generation for hydrogen fuel cells. “With our research, we hope to build a clean, sustainable, society, one brick at a time,” concludes Prof. Negishi.

Exploring human-body communications with binaural hearing aids

Posted on by Tokyo University of Science

Wearable technology seems all poised to take over next-generation electronics, yet most wireless communication techniques are not up to the task. To tackle this issue, scientists from the Tokyo University of Science, Japan, delved deep into human-body communications (HBC), in which human tissue is used as the transmission medium for electromagnetic signals. Their findings pave the way to more efficient and safer head-worn devices, such as binaural hearing aids and earphones.

To explore the full potential of HBC, researchers from Japan, including Dr. Dairoku Muramatsu from Tokyo University of Science and Professor Ken Sasaki from The University of Tokyo focused on using HBC for a yet unexplored use: binaural hearing aids.

Such hearing aid devices come in pairs—one for each ear—and greatly improve intelligibility and sound localization for the wearer by communicating with each other to adapt to the sound field. Because these hearing aids are in direct contact with the skin, they made for a perfect candidate application for HBC.

In a recent study, which was published in the journal Electronics, the researchers investigated, through detailed numerical simulations, how electric fields emitted from an electrode in one ear distribute themselves in the human head and reach a receiving electrode on the opposite ear, and whether it could be leveraged in a digital communication system. In fact, the researchers had previously conducted an experimental study on HBC with real human subjects, the results of which were also published in Electronics.

Using human-body models of different degrees of complexity, the researchers first determined the best representation to ensure accurate results in their simulations and then once this was settled, they proceeded to explore the effects of various system parameters and characteristics.

Dr. Muramatsu SAYS, “We calculated the input impedance characteristics of the transceiver electrodes, the transmission characteristics between transceivers, and the electric field distributions in and around the head. In this way, we clarified the transmission mechanisms of the proposed HBC system.”

Finally, with these results, they determined the best electrode structure out of the ones they tested. They also calculated the levels of electromagnetic exposure caused by their system and found that it would be completely safe for humans, according to modern safety standards.

Overall, this study showcases the potential of HBC and extends the applicability of this promising technology. After all, hearing aids are but one of all modern head-worn wireless devices. For example, HBC could be implemented in wireless earphones to enable them to communicate with each other using far less power.

Moreover, because the radio waves used in HBC attenuate quickly outside of the body, HBC-based devices on separate people could operate at similar frequencies in the same space without causing noise or interference.

“With our results, we have made great progress towards reliable, low-power communication systems that are not limited to hearing aids but also applicable to other head-mounted wearable devices. Not just this, accessories such as earrings and piercings could also be used to create new communication systems,” concludes Dr. Muramatsu.

Difficulties in reading recent Japanese names

Posted on by Tokyo University of Science

Assistant Professor Yuji Ogihara from the Tokyo University of Science analyzed approximately 8,000 names of infants born between 2004 and 2018 obtained from the database of a life insurance company. He first chose four recent common names for boys and girls each (Boys: “大翔,” “陽翔,” “翔,” “颯,” Girls: “結愛,” “陽菜,” “愛,” “杏”) on the basis of popularity rankings for each year.

He then comprehensively surveyed all their readings and calculated the ratio and number of ways to read each name. These results were published on June 21, 2021 in the international journal Humanities and Social Sciences Communications.

Assistant Professor Ogihara discovered that there are at least 18 ways to read “大翔” (Figure 2), and at least 14 ways to read “結愛” (Figure 3). Even single-character names like “颯,” and “杏,” had seven and five readings, respectively. The readings each differed greatly in pronunciation, length, and meaning. Assistant Professor Ogihara showed that the
other names have many readings, too.

He further found that parents were not only using the common readings of each character, but also using readings that do not exist for a character or using a character for its meaning and imagery. For example, “大翔” was also read as “Tsubasa”(meaning “wing”). Neither “大” nor “翔” formally have “Tsubasa” as a reading. “翔” is read as “Tsubasa” because it has the meanings “flap” and “fly,” and a reading associated with the imagery of the character is observed. The character “大” is given, but not pronounced, and the meaning “to flap broadly” is obtained. Hence, the character is only added for its imagery or meaning.

Assistant Professor Ogihara also saw a pattern of abbreviating common readings. For example, “大翔” was read as “Taishi.” “大” has the reading “tai,” and “翔” has the reading “shou.” “Shou” was abbreviated to “shi” and combined with “tai.” He also found instances where the meanings of characters are read in foreign languages. Take “結愛 Yura,” for example. While “結” comes from the common reading “yu(u),” “愛” is generally not read as “ra,” but because “愛” means “love” (rabu) in English, it is possible to omit the “bu” and use it as “ra.”

In this study, Assistant Professor Ogihara systematically analyzed actual name data and empirically investigated the difficulty of correctly reading Japanese names. The investigation of these difficulties contributes to deepening our understanding of naming practices and the characteristics of names, not only in Japan but in the Sinosphere, which includes East and Southeast Asia.