Tag: Tokyo University of Science

Consistent manufacturing and production of monoclonal antibodies (mAbs) is critical, and their functional profiles depend on cell culture conditions. Now, researchers from Japan have investigated the role of intracellular polyamines on N-glycan profiles of mAbs. They found that polyamine depletion led to an ER stress response in CHO cells, leading to an increase in galactosylation of mAbs. Supplementation of spermidine recovered N-glycan profiles. These findings will contribute to the stable production of antibody-based drugs.

Monoclonal antibodies (mAbs) are laboratory-designed proteins that mimic the immune system’s antibodies. To date, many therapeutic mAbs belonging to the immunoglobulin G (IgG) class of antibodies, have been approved for the treatment of cancer and autoimmune diseases. Cell lines such as the Chinese hamster ovary (CHO) cells are generally used to produce mAbs. Notably, the production and manufacture of mAbs are regulated by critical quality attributes (CQAs) to ensure their safety and efficacy in treatment.

An important CQA for mAbs is the N-linked glycosylation present at a specific position (Asn297). N-linked glycans consist of N-acetylglucosamine (GlcNAc), mannose (Man), fucose (Fuc), galactose (Gal), and sialic acid. The heterogeneity of the N-linked glycan profiles of mAbs can be attributed to the different numbers and linkages of additional saccharides. The composition of N-linked glycans affects the overall therapeutic efficacy, targeting ability, and immune-specificity of these antibodies. For example, antibody-dependent cellular cytotoxicity (ADCC) is influenced by the fucosylation and galactosylation of N-linked glycans. Complement-dependent cytotoxicity (CDC) is also affected by the galactosylation and sialylation of N-linked glycans. Hence, it’s crucial to meticulously regulate N-linked glycan profiles throughout the manufacturing process because the heterogeneity of the N-linked glycan profile of mAbs depends on the cell culture duration and changes in nucleotide sugars and glycosylation enzyme levels.

Recently, Dr. Kyohei Higashi, Associate Professor at Tokyo University of Science (TUS) in Japan, along with a team of researchers including Dr. Rin Miyajima and Dr. Masahiro Komeno, conducted a study to explore the effects of polyamines on N-linked glycan profiles of mAbs in CHO DP-12 cells. Their work was made available online on November 3, 2023 in the Journal of Biotechnology.

“Because the carbohydrate structure of mAbs changes depending on the state of the cells, we were interested in investigating the relationship between intracellular polyamines and the carbohydrate structure of mAbs from CHO cells.” explained Dr. Higashi, when asked about the motivation behind the research.

Polyamines (putrescine, PUT; spermidine, SPD; and spermine, SPM) are present in millimolar concentrations in all living organisms and play essential roles in normal cell growth and differentiation. PUT, SPD, and SPM contained two, three, and four amino groups, respectively. PUT is synthesized from ornithine (ORN) by ornithine decarboxylase (ODC), a rate-limiting enzyme in the polyamine biosynthesis pathway. SPD is synthesized from putrescine by spermidine synthase, and spermine is synthesized from spermidine by spermine synthase. Intracellular polyamine levels are regulated at various steps, including synthesis, degradation, and transport, and are affected by external stimuli, aging, and diseases. Because CHO cells lack arginase activity to produce ORN from arginine, they cannot produce polyamines in serum-free media, resulting in a decrease in intracellular polyamine levels, which causes a low growth rate and cell viability during long-term cultivation.

Intracellular polyamine levels can also be decreased by treatment with α-difluoromethylornithine (DFMO), an inhibitor of ODC. The depletion of intracellular polyamines by DFMO can be reversed by the addition of SPD to the growth media of CHO cells.

Upon introducing DFMO to the CHO cells, the team observed that IgG antibody galactosylation surged, along with an increase in the levels of β1,4-galactosyl transferase 1 (B4GALT1) mRNA. This mRNA is pivotal in governing the IgG galactosylation mechanism within CHO cells. What’s more, IgG production decreased by approximately 30% in DFMO-treated cells.

Dr. Higashi hypothesized that the decrease in IgG production was a result of endoplasmic stress (ER) stress response caused by polyamine depletion. During ER stress response, protein folding ceases, resulting in the arrest of the normal function of cells. Chaperone proteins assist in the correct folding of other protein classes and play a crucial role under both normal and stress conditions. The results of the ER stress response study confirmed the increased expression levels of chaperones for glycoprotein folding, in polyamine-depleted cells.

The team further observed that upon using tunicamycin, an ER stress inducer inhibiting N-glycosylation, ER stress from polyamine depletion triggered B4GALT1 mRNA expression, increasing IgG galactosylation in CHO cells.

The ability to maintain antibody glycosylation profiles via polyamine modulation has numerous implications. Controlled glycosylation is crucial for optimizing therapeutic proteins, such as antibodies, ensuring the stable production of antibodies in a uniform manner of biological activities, and potentially decreasing the manufacturing cost. Supplementation of polyamine could be accomplished by the addition only of SPD to serum-free medium, offer an easy and costless method to maintain the glycan structure of mAbs produced by CHO cells cultured in the serum-free medium. This insight might influence cell line development and bioproduction, facilitating the creation of biosimilars.

“Introducing polyamines, particularly SPD, to serum-free culture medium for CHO cells may contribute to consistent manufacturing and quality control of antibody production. We hope that this research will contribute to the stable production of antibody drugs and lead to lower drug prices” concludes Dr. Higashi.

Data Assimilation (DA) is an important mathematical method for predicting turbulent flows for weather forecasting. However, the origins of the critical length scale, a crucial parameter in this method, and its dependence on the Reynolds number are not well understood. Now, researchers have developed a novel theoretical framework that treats DA as a stability problem to explain this parameter. This framework can contribute significantly to turbulence research and inspire novel data-driven methods to predict turbulence.

Weather forecasting is important for various sectors, including agriculture, military operations, and aviation, as well as for predicting natural disasters like tornados and cyclones. It relies on predicting the movement of air in the atmosphere, which is characterized by turbulent flows resulting in chaotic eddies of air. However, accurately predicting this turbulence has remained significantly challenging owing to the lack of data on small-scale turbulent flows, which leads to the introduction of small initial errors. These errors can, in turn, lead to drastic changes in the flow states later, a phenomenon known as the chaotic butterfly effect.

To address the challenge of limited data on small-scale turbulent flows, a data-driven method known as Data Assimilation (DA) has been employed for forecasting. By integrating various sources of information, this approach enables the inference of details about small-scale turbulent eddies from their larger counterparts. Notably, within the framework of DA methods, a crucial parameter known as the critical length scale has been identified. This critical length scale represents the point below which all relevant information about small-scale eddies can be extrapolated from the larger ones. Reynold’s number, an indicator of the turbulence level in fluid flow, plays a pivotal role in this context, with higher values suggesting increased turbulence. However, despite the consensus generated by numerous studies regarding a common value for the critical scale, an explanation of its origin and its relationship with Reynold’s number remains elusive.

To address this issue, a team of researchers, led by Associate Professor Masanobu Inubushi from the Tokyo University of Science, Japan, has recently proposed a theoretical framework. They treated the process of DA as a stability problem. “By considering this turbulence phenomenon as ‘synchronization of a small vortex by a large vortex’ and by mathematically attributing it to the ‘stability problem of synchronized manifolds,’ we have succeeded in explaining this critical scale theoretically for the first time,” explains Dr. Inubushi. The letter, published in Physical Review Letters on December 18, 2023, is co-authored by Professor Yoshitaka Saiki from Hitotsubashi University, Associate Professor Miki U. Kobayashi from Rissho University, and Professor Susumo Goto from Osaka University.

To this end, the research team employed a cross-disciplinary approach by combining chaos theory and synchronization theory. They focused on an invariant manifold, termed as the DA manifold, and conducted a stability analysis. Their findings revealed that the critical length scale is a key condition for DA; and is characterized by transverse Lyapunov exponents (TLEs), which ultimately dictate the success or failure of the DA process. Additionally, based on a recent discovery showing Reynolds number dependence of maximal Lyapunov exponent (LE) and the relation of TLEs with maximal LE, they concluded that the critical length scale increases with the Reynolds number, clarifying the Reynolds number dependence of the critical length scale.

Emphasizing the importance of these findings, Dr. Inubushi says, “This new theoretical framework has the potential to significantly advance turbulence research in critical problems such as unpredictability, energy cascade, and singularity, addressing a field that physicist Richard P. Feynman once described as ‘one of the remaining difficulties in classical physics.’”

In summary, the proposed theoretical framework not only enhances our understanding of turbulence, but also paves the way for novel data-driven methods that can enhance the accuracy and reliability of weather forecasting.

Let us hope for more accurate weather predictions soon!

Falls are a serious risk for older individuals and people with compromised balance. However, there are no convenient devices to train one’s reactive posture control against unexpected perturbations outside of clinical settings. To tackle this issue, researchers from Japan have developed a lightweight wearable device to perform balance exercises at home. The experimental results showcase the potential of this device to improve postural control, thus helping prevent falls and fall-related injuries.

Maintaining balance and posture is quite a complex skill, even though it comes naturally to most people. However, postural control tends to worsen with age due to various reasons, such as muscle weakness coupled with changes in vision and sensory input. This explains why older people are much more prone to falling and suffering fall-related injuries than younger individuals. Approximately 40% of older individuals have been reported to fall at least once a year.

In this regard, over the past few decades, scientists have found that postural control can be improved through various exercises, which in turn helps prevent falls. It is possible to train and cultivate the ability to perform compensatory postural adjustments (CPAs) to counteract the effects of unexpected external perturbations. Although scientists have come up with specialized devices to perform balance exercises involving unexpected perturbations, these machines are generally bulky, expensive, and complex to use, rendering them suitable for clinical settings only.

But could there be a more practical way to perform these exercises comfortably at home? In a recent study published in IEEE Journal of Translational Engineering in Health and Medicine on 31 August 2023, a research team led by Assistant Professor Masataka Yamamoto from Tokyo University of Science (TUS), Japan, and including Professor Hiroshi Takemura, Mr. Daiki Yoshikawa, and Mr. Taku Washida from TUS, as well as Professor Koji Shimatani from the Prefectural University of Hiroshima, explore this question. For their research, the researchers developed an innovative wearable balance exercise device (WBED) and investigated its effects on CPAs and reactive postural control.

The proposed wearable device uses two pneumatic artificial muscles (PAMs) to generate unexpected perturbations. These PAMs, which resemble a pair of hollow shoulder straps or suspenders, can be forced to extend or contract by regulating the air pressure inside them. For this purpose, the WBED includes a set of electronically controlled valves connected to a can of compressed gas. This enables a computer program or smartphone application to control the valves and quickly fill or empty either PAM with gas, producing a force that pulls the user sideways in a specific direction.

To test whether WBED can truly improve reactive postural control, the researchers recruited 18 healthy adult males and divided them randomly into two groups: WBED and sham. All participants first underwent an evaluation of reactive balance. They had to hold a tandem stance for one minute while air cylinders on both sides of the hips pushed them laterally at unpredictable moments. The participants in the WBED group then performed a few rounds of balance training using the proposed device, while the sham group underwent the same exercises without unexpected perturbation. Lastly, a second evaluation was performed to check for improvements in postural control.

The researchers measured several variables as outcomes during the evaluations, including peak displacement, time at peak displacement, peak velocity, and root mean square of the soles’ center of pressure. Notably, participants in the WBED group exhibited lower displacement and peak velocity after exercising with the device. “Our results prove that perturbation-based balance exercises using WBED immediately improve the subjects’ reactive postural control,” remarks Dr. Yamamoto, satisfied with their findings. “Wearable exercise devices, such as the proposed WBED, could contribute to the prevention of falls and fall-related injuries.”

In the near future, the proposed device could revolutionize how people with a high tendency to fall perform balance training, especially in countries with a steadily aging population like Japan. “We designed WBED to be lightweight, portable, and easy to use both at home and in clinical settings. It weighs only 0.9 kg and takes less than three minutes to put on,” highlights Dr. Yamamoto. By training regularly with WBED, older individuals and people undergoing physical therapy can efficiently improve postural control and responsiveness, which in turn would prevent falls and improve their overall health. Notably, WBED could also be useful for athletes who want to improve their balance.

Let us hope that wearable devices become a mainstay in balance training and health care monitoring, providing a boost to the Internet of Things technology!

Sodium- and potassium-ion batteries are promising next-generation alternatives to the ubiquitous lithium-ion batteries (LIBs). However, their energy density still lags behind that of LIBs. To tackle this issue, researchers from Japan explored an innovative strategy to turn hard carbon into an excellent negative electrode material. Using inorganic zinc-based compounds as a template during synthesis, they prepared nanostructured hard carbon, which exhibits excellent performance in both alternative batteries.

Lithium-ion batteries (LIBs) are, by far, the most widely used type of rechargeable batteries, spanning numerous applications. These include consumer electronics, electric vehicles (e.g., Tesla cars), renewable energy systems, and spacecrafts. Although LIBs deliver the best performance in many aspects when compared to other rechargeable batteries, they have their fair share of disadvantages. Lithium is a rather scarce resource, and its price will rise quickly with its availability going down in the future. Moreover, lithium extraction and improperly discarded LIBs pose huge environmental challenges as the liquid electrolytes commonly used in them are toxic and flammable.

The shortcomings of LIBs have motivated researchers worldwide to look for alternative energy storage technologies. Sodium (Na)-ion batteries (NIBs) and potassium-ion batteries (KIBs) are two rapidly emerging options that are cost-efficient as well as sustainable. Both NIBs and KIBs are projected to be billion-dollar industries by the end of the decade. Governments across the world, including that of the US, Austria, Hong Kong, Germany, and Australia, are promoting research and innovation in this field. Moreover, companies such as Faradion Limited, TIAMAT SAS, and HiNa Battery Technology Co. Ltd., are investing heavily in this technology. Both Contemporary Amperex Technology Co. Limited and Build Your Dreams are expected to introduce electric vehicle battery packs with NIBs soon.

Unfortunately, however, the capacity of the electrode materials used in NIBs and KIBs still lags behind that of LIBs. Against this backdrop, a research team led by Professor Shinichi Komaba from Tokyo University Science (TUS), Japan, has been working to develop groundbreaking high-capacity electrode materials for NIBs and KIBs. In their latest study, published in Advanced Energy Materials on November 9, 2023, they report a new synthesis strategy for nanostructured “hard carbon” (HC) electrodes that deliver unprecedented performance. The study was co-authored by Mr. Daisuke Igarashi, Ms. Yoko Tanaka, and Junior Associate Professor Ryoichi Tatara from TUS, and Dr. Kei Kubota from the National Institute for Materials Science (NIMS), Japan.

But what is HC and why is it useful for NIBs and KIBs? Unlike other forms of carbon, such as graphene or diamond, HC is amorphous; it lacks a well-defined crystalline structure. Additionally, it is strong and resistant. In an earlier 2021 study, Prof. Komaba and his colleagues had found a way to use magnesium oxide (MgO) as a template during the synthesis of HC electrodes for NIBs, altering their final nanostructure. The process had led to the formation of nanopores within the electrodes upon MgO removal, which, in turn, had vastly increased their capacity to store Na+ ions.

Motivated by their previous findings, the researchers explored whether compounds made from zinc (Zn) and calcium (Ca) could also be useful as nano-templates for HC electrodes. To this end, they systematically investigated different HC samples made using zinc oxide (ZnO) and calcium carbonate (CaCO3) and compared their performance with the ones synthesized using magnesium oxide (MgO).

Preliminary experiments showed that ZnO was particularly promising for the negative electrode of NIBs. Accordingly, the researchers optimized the concentration of ZnO embedded in the HC matrix during synthesis, demonstrating a reversible capacity of 464 mAh g–1 (corresponding to NaC4.8) with a high initial Coulombic efficiency of 91.7% and a low average potential of 0.18 V vs. Na+/Na.

The team achieved remarkable results by incorporating this powerful electrode material into an actual battery. “The NIB fabricated using the optimized ZnO-templated HC as the negative electrode exhibited an energy density of 312 Wh kg–1,” highlights Prof. Komaba. “This value is equivalent to the energy density of certain types of currently commercialized LIBs with LiFePO4 and graphite and is more than 1.6 times the energy density of the first NIBs (192 Wh kg–1), which our laboratory reported back in 2011.” Notably, the ZnO-templated HC also exhibited a significant capacity of 381 mAh g–1 when incorporated into a KIB, further showcasing its potential.

Taken together, the results of this study show that using inorganic nanoparticles as a template to control the pore structure may provide an effective guideline for the development of HC electrodes. “Our findings prove that HCs are promising candidates for negative electrodes as an alternative to graphite,” concludes Prof. Komaba.

In turn, this could make NIBs viable for practical applications, such as the development of sustainable consumer electronics and electric vehicles as well as low carbon footprint energy storage systems for storing energy from solar and wind farms.

G protein-coupled receptors (GPCRs) are the largest and most diverse group of cell surface proteins in humans. These receptors, which can be seen as ‘traffic directors,’ transmit signals from the outside to the inside of cells and are involved in many physiological processes. Given their prominent roles in cellular communication, cell growth, immune responses, and sensory perception, many drugs have been developed to target GPCRs, for the treatment of conditions such as asthma, allergies, depression, hypertension, and heart disease. In fact, more than 300 GPCR-related drugs are currently in clinical trials, 36% of which target over 60 novel GPCR targets without an already-approved drug. Moreover, drugs that target GPCRs account for as much as 27% of the global market share of therapeutic drugs, with aggregated sales close to US$890 billion between 2011 and 2015. Thus, any technique that could accelerate research on GPCRs is likely to trigger a large ripple effect, ultimately bringing more effective treatments to millions of people.

Today, approaches such as cryo-electron microscopy, optogenetics, computational approaches and artificial intelligence, biosensors and label-free technologies, and single-cell technologies are being explored for GPCR drug discovery and development. Among them, the single-cell approach based on yeast is one of the most useful platforms to study GPCRs. Besides its widespread application in beer and bread making, the yeast species Saccharomyces cerevisiae has a long history of being used as a host to research human derived GPCRs. Although some GPCRs can be engineered to enhance their stability and function to facilitate experiments, most GPCRs do not function well in yeast cells. This long-standing problem has greatly slowed progress in our understanding of GPCRs and the development of new drugs that target them.

Against this backdrop, a research team from Tokyo University of Science (TUS), Japan, recently came up with an innovative strategy to restore the activity of human derived GPCR human histamine 3 (H3R) in S. cerevisiae. Their study, published in Volume 13 of Scientific Reports on September 26, 2023, was led by Associate Professor Mitsunori Shiroishi and co-authored by Ms. Ayami Watanabe and Ms. Ami Nakajima, all from TUS.

“H3R is mainly expressed in the nervous system. It is involved in cognitive function, and its inhibition is associated with the therapeutic outcomes of various conditions, such as ADHD, schizophrenia, Alzheimer’s disease, and narcolepsy,” explains Dr. Shiroishi. Through preliminary experiments, the team showed that H3R becomes non-functional when expressed in yeast.

To restore its function, the research team utilized a technique called error-prone polymerase chain reaction to introduce random mutations in the H3R gene. After producing a random mutant library of H3R, they introduced modified DNA segments into yeast cells and cultivated them in the presence of an H3R agonist—a compound that binds to H3R and sets off a measurable response. By screening through multiple cultures, the researchers obtained four mutants in which the normal activity of H3R was restored. These mutants responded exclusively to a type of yeast strain that harbors certain G-chimera proteins. The mutations responsible for the restored activity were located near the amino acid sequence motifs important for GPCR activation.

This innovative approach to study GPCRs could have profound implications, particularly in the fields of medicine and cell biology. “Our research could help elucidate the function of GPCRs and may even lead to the development of drugs with fewer side effects, as well as bolster drug discovery for diseases for which there is currently no treatment,” remarks Dr. Shiroishi. There are many therapeutic areas where GPCR-targeting drugs are being actively developed, including neurological disorders like Alzheimer’s and schizophrenia, cardiovascular diseases such as hypertension and heart failure, various types of cancer, and metabolic disorders.

A deeper understanding of GPCR variations and how they impact individuals differently could also lead to new approaches to personalized medicine. Tailoring GPCR-targeted drugs to an individual’s genetic makeup and their specific disease profile may greatly improve treatment outcomes. Furthermore, generic GPCR treatments reaching a vast number of people worldwide might also become a reality, which would reduce the burden on healthcare systems.

We are certain that the findings of this study will pave the way to a healthier future for everyone.

The 4-point Optimal Point Charge (OPC) and 3-point OPC (OPC3) models are highly accurate water models, used extensively in molecular simulations to reproduce the properties of bulk water. However, there are no reports on whether these models can accurately reproduce the viscosity of water. Recently, a researcher from Japan tested the performance of the OPC and OPC3 models by evaluated their shear viscosities and comparing them to experimental results.

Water is one of the most abundant substances on Earth and partakes in countless biological, chemical, and ecological processes. Thus, understanding its behavior and properties is essential in a wide variety of scientific and applied fields. To do so, researchers have developed various water models to reproduce the behavior of bulk water in molecular simulations. While these simulations can provide valuable insights into the specific properties of water, selecting an appropriate model for the system under study is crucial. Today, two water models have become very popular among biomolecular researchers: the 4-point Optimal Point Charge (OPC) and 3-point OPC (OPC3) models. These models are known for their ability to reproduce several properties of water with high accuracy, including density, heat of vaporization, and dielectric constant. However, there is limited information on whether OPC and OPC3 water models can accurately predict the shear viscosity of water.

The viscosity of water greatly affects how water molecules interact with other substances and surfaces, dictating critical phenomena such as diffusion and absorption. This affects the texture and taste of foods and beverages, as well as how oils and liquids interact with food during cooking. More importantly, the viscosity of water needs to be considered when designing and manufacturing pharmaceutical products, as well as many types of lubricants and polymeric materials. In addition, it influences how water and water-based solutions flow through small tubes, such as those in our circulatory system and in microfluidic devices.

Recently, Associate Professor Tadashi Ando from Tokyo University of Science conducted a study to test the performance of the OPC and OPC3 models, by evaluating their shear viscosities and comparing the values to the experimental calculations. These findings were published in Volume 159, Issue 10 of The Journal of Chemical Physics on September 14, 2023.

First, Dr. Ando set up molecular dynamics simulations of up to 2,000 water molecules using popular water models, including OPC, OPC3, and variants of the Transferable Intermolecular Potential 3-point (TIP3P) and 4-point (TIP4P) models. Next, he used an approach known as the Green-Kubo formalism—a commonly used method from statistical mechanics to study viscosity and heat conduction in various materials— to calculate the viscosity of the models.

The calculated viscosities for both OPC and OPC3 water models were very close to each other for temperatures ranging from 273 K to 373 K. Notably, for temperatures above 310 K, the viscosity predicted by these models was very close to that predicted by previous experimental findings. However, this was not the case at lower temperatures. Dr. Ando explains, “Compared to other water models, the performance of the OPC and OPC3 models in terms of predicting the shear viscosity was lower than that of TIP4P and TIP3P variants, but only for temperatures below 293 K.” Notably, at 273 K and 293 K, the shear viscosities of the two models were around 10% and 20% lower, respectively, as compared to those derived experimentally.

In addition to viscosity, Dr. Ando also assessed the performance of the OPC and OPC3 models for predicting other important water properties, such as surface tension and self-diffusion. The performance of OPC and OPC3 for these properties was remarkably accurate. “Based on the results of this study, along with those from previous reports, we can conclude that the OPC and OPC3 are among the best nonpolarizable water models at present, accounting for the various static and dynamic properties of water,” highlights Dr. Ando.

Overall, this study provides a thorough understanding of the advantages and limitations of water models. With any luck, this will help scientists polish these models to make them even more useful across various technological fields!

Aqueous potassium-ion batteries are a promising alternative to lithium-ion batteries owing to their safety and low cost. However, not much is known about the properties of the solid-electrolyte interphases (SEI) that form between the electrode and the aqueous electrolyte. To address this knowledge gap, researchers from Japan have now conducted a study using advanced scanning electrochemical microscopy and operando electrochemical mass spectrometry. Their findings provide a deeper understanding of SEI in next-generation batteries.

Lithium-ion batteries (LIBs) have become immensely popular as the go-to power source for a wide variety of electronic devices and vehicles over the past two decades. Although it is hard to overstate the transformative effects that LIBs have had on modern societies, this technology has a fair share of disadvantages that cannot be ignored any further. These include the limited availability of lithium as well as safety and environmental concerns. These drawbacks have motivated scientists around the world to look for alternative battery technologies, such as aqueous batteries. Potassium-ion batteries (KIBs) are a prominent example; these batteries are made from abundantly available materials and are much safer than LIBs. Moreover, KIBs can utilize a water-in-salt electrolyte (WISE), which makes them more stable thermally and chemically.

However, the prevention of hydrogen evolution at the negative electrode for its stabilization is a major challenge in high-voltage aqueous batteries. While solid-electrolyte interphases (SEI) that form between these electrodes and the electrolyte solution help stabilize the electrodes in LIBs (by preventing electrolyte decomposition and self-discharge of the batteries), they have been scarcely researched in the context of KIBs.

To address this major knowledge gap, a research team from Tokyo University of Science– (TUS), Japan, has recently conducted a pioneering study to gain insights into SEI formation and their properties in WISE-based KIBs. Their findings were published online in the journal Angewandte Chemie International Edition on August 18, 2023. The study, led by TUS Professor Shinichi Komaba, is co-authored by Junior Associate Professor Ryoichi Tatara, Dr. Zachary T. Gossage, and Ms. Nanako Ito, all from TUS.

The researchers mainly employed two advanced analytical techniques—scanning electrochemical microscopy (SECM) and operando electrochemical mass spectrometry (OEMS)—to observe how SEI forms and reacts in real time during the operation of a KIB with a 3,4,9,10-perylenetetracarboxylic diimide negative electrode and 55 mol/kg K(FSA)0.6(OTf)0.4∙1H2O, a WISE developed by the team in a previous study.

The experiments revealed that SEI forms a passivating layer in WISE akin to that seen in LIBs, with slow apparent electron transfer rates, helping suppress hydrogen evolution. This can ensure stable performance and higher durability of KIBs. However, the researchers observed that the coverage of the SEI layer was incomplete at higher operating voltages, leading to hydrogen evolution.

Taken together, the results reveal the need to explore potential avenues to enhance SEI formation in future aqueous batteries. “While our results reveal interesting details on the properties and stability of SEI found in one particular WISE, we should also focus on reinforcing the SEI network to achieve improved functionality,” comments Prof. Komaba. “SEI could perhaps be improved by the development of other electrolytes that produce unique SEIs, but also through the incorporation of electrolyte additives or electrode surface pretreatment.”

This study also highlights the power of SECM and OEMS for gaining a solid understanding of electrode–electrolyte interactions in next-generation batteries. “These techniques provide a powerful means for tracking the development, coverage, ion transfer, and stability of SEI and can easily be adapted for a variety of electrolytes and electrodes,” explains Prof. Komaba. “We hope that this work encourages other researchers to further explore SECM and OEMS as advanced characterization methods that can be incorporated with traditional battery measurements to gain deeper insights.”

The development of aqueous batteries such as KIBs will be instrumental for sustainable societies in the future, since they could replace the expensive and hazardous LIBs currently used in electric vehicles, smart grids, renewable energy systems, and marine applications. By making energy storage more accessible, aqueous batteries will aid the transition toward carbon-neutral energy generation, paving the way for a greener future.

With any luck, further studies will lead us to promising LIB alternatives soon!

Scientists identify a fungal strain that transforms patulin, a dangerous mycotoxin sometimes found in fruits, into less toxic byproducts

Patulin is a harmful mycotoxin produced by fungi typically found in damaged fruits, including apples, pears, and grapes. In a recent breakthrough, researchers from Japan identified a new filamentous fungal strain that can degrade patulin by transforming it into less toxic substances. Their findings provide important insights into the degradation mechanisms for patulin found in nature, and can lead to new ways of controlling patulin toxicity in our food supplies.

Patulin (C7H6O4), a mycotoxin produced by several types of fungi, is toxic to a variety of life forms, including humans, mammals, plants, and microorganisms. In particular, environments lacking proper hygienic measures during food production are susceptible to patulin contamination as many of these fungi species tend to grow on damaged or decaying fruits, specifically apples, and even contaminate apple products, such as apple sauce, apple juice, jams, and ciders.

Responsible for a wide variety of health hazards, including nausea, lung congestion, ulcers, intestinal hemorrhages, and even more serious outcomes, such as DNA damage, immunosuppression, and increased cancer risk, patulin toxicity is a serious concern worldwide. As a result, many countries have imposed restrictions on the permitted levels of patulin in food products, especially baby foods as infants are more vulnerable to the effects of patulin.

Treatment of patulin toxicity include oxygen therapy, immunotherapy, detoxification therapy, and nutrient therapy. However, as prevention is often better than cure, scientists have been on the lookout for efficient ways to mitigate patulin toxicity in food products. To this end, a research team including Associate Professor Toshiki Furuya from Tokyo University of Science (TUS) in Japan, recently screened for soil microorganisms that can potentially help keep patulin toxicity in check. Their study, published online in Volume 12, Issue 4 of MicrobiologyOpen on 11 August 2023, was co-authored by Ms. Megumi Mita, Ms. Rina Sato, and Ms. Miho Kakinuma, all from TUS.

The team cultured microorganisms from 510 soil samples in a patulin-rich environment, looking for those that would thrive in presence of the toxin. Next, in a second screening experiment, they used high-performance liquid chromatography (HPLC) to determine the survivors that were most effective in degrading patulin into other less harmful chemical substances. Accordingly, they identified a filamentous fungal (mold) strain, Acremonium sp. or “TUS-MM1,” belonging to the genera Acremonium, that fit the bill.

The team then performed various experiments to shed light on the mechanisms by which TUS-MM1 degraded patulin. This involved incubating the mold strain in a patulin-rich solution and focusing on the substances that gradually appeared both inside and outside its cells in response to patulin over time.

One important finding was that TUS-MM1 cells transformed any absorbed patulin into desoxypatulinic acid, a compound much less toxic than patulin, by adding hydrogen atoms to it. “When we started this research, only one other filamentous fungal strain had been reported to degrade patulin,” comments Dr. Furuya. “However, prior to the present study, no degradation products had ever been identified. In this regard, to our knowledge, TUS-MM1 is the first filamentous fungus shown to be capable of degrading patulin into desoxypatulinic acid.”

Moreover, the team found that some of the compounds secreted by TUS-MM1 cells can also transform patulin into other molecules. By mixing patulin with the extracellular secretions of TUS-MM1 cells and using HPLC, they observed various degradation products generated from patulin. Encouragingly, experiments on E. coli bacterium cells revealed that these products are significantly less toxic than patulin itself. Through further chemical analyses, the team showed that the main agent responsible for patulin transformation outside the cells was a thermally stable but highly reactive compound with a low molecular weight.

Overall, the findings of this study take us a step closer toward efficient solutions for controlling the levels of patulin in food. Dr. Furuya speculates: “Elucidating the pathways via which microorganisms can degrade patulin would be helpful not only for increasing our understanding of the underlying mechanisms in nature but also for facilitating the application of these organisms in biocontrol efforts.”

Let us hope that these efforts will pave the way for safer fruit-based foods and beverages!

Researchers from Japan propose a novel non-contact method that utilizes subtle color changes on the face to estimate heart rates

Heart rate, an essential indicator of overall health and well-being, is traditionally measured by counting the number of cardiac pulses within a specific timeframe. Existing methods, however, require physical contact with the patient, which can lead to discomfort and skin-related issues. Now, researchers from Japan introduce an innovative non-contact approach that analyzes subtle color changes on the face to enable highly accurate heart rate estimation, even in scenes with ambient light fluctuations.

Heart rate (HR) estimation is an essential component of health monitoring, and provides useful insights regarding the physiological and emotional state of humans. In the past decade or so, researchers have explored newer approaches for contactless HR estimation, primarily to overcome the discomfort or dermatitis associated with conventional methods that require physical contact. Non-contact HR estimation using cameras is an example of one such method. The method focuses on the blood volume pulse (BVP), that causes slight temporal changes in facial skin color captured in videos. By examining these color variations, it becomes possible to estimate HR. However, due to the small magnitude of these color changes, the accuracy of HR estimation is adversely affected by facial movements, ambient lighting variations, and noise.

To address these challenges, a team of researchers from Japan have now developed a novel method that leverages the temporal characteristics of the blood pulse. Importantly, it builds on the ability of the pulse to exhibit quasi-periodic behavior, which distinguishes it from noise artifacts. The study was led by Dr. Yoshihiro Maeda, Junior Associate Professor, from the Department of Electrical Engineering at the Tokyo University of Science and is published in Volume 11 of IEEE Access journal on 9 June 2023. Professor Takayuki Hamamoto and Kosuke Kurihara from the Tokyo University of Science and Associate Professor Daisuke Sugimura from the Department of Computer Science, Tsuda University, were also a part of this study.

The proposed method utilizes dynamic mode decomposition (DMD), a technique that analyzes spatio-temporal structures in multi-dimensional time-series signals. It also employs adaptive selection of the optimal spatio-temporal structure based on medical knowledge of HR frequencies. “Our method, unlike previous applications of DMD, effectively models and extracts the BVP signal by incorporating physics-informed DMD in a time-delay coordinate system, taking into account the nonlinearity and quasi-periodicity of the BVP dynamics,” explains Kosuke Kurihara, a Ph.D. student.

The proposed method relies solely on tracking time-series data from videos of a person’s face, eliminating the need for any attached detectors on the person’s body. In this method, the video time-series of the face, monitoring continuous changes, are converted into RGB time-series signals, which helps in extracting information of blood volume changes occurring beneath the skin. After effectively dealing with noise or misinformation that might creep into the data, the observed RGB signals are then converted to pulse wave information data.

Using the DMD method in a time-delayed coordinate system with conservative dynamics modeling, pulse waves containing major and accurate information can be extracted to estimate HR.

To demonstrate the efficacy of this method, the researchers used 67 facial videos from three publicly available datasets – namely TokyoTech Remote PPG dataset, MR-NIRP dataset, and UBFC-RPPG dataset. The results of this method were then compared with other non-contact HR estimation methods, including DistancePPG, SparsePPG, SAMC, Hierarchical, and MTTS-CAN.

Interestingly, the proposed method adaptively selects the dynamic mode that contains the most pulse wave components, based on the knowledge of the typical range of pulse wave components. As a result, the method showed a 36.5% improvement in estimation accuracy compared to conventional methods, especially in scenes with ambient light fluctuations.

“This achievement is expected to play a significant role as a fundamental technology for vital monitoring systems in the medical and fitness fields. The breakthrough contactless method holds great potential for non-contact heart rate estimation in various applications, such as remote health monitoring and physiological assessments,” concludes Dr. Maeda. The research findings provide new possibilities for enhancing healthcare technologies and improving overall patient comfort and well-being. Going ahead, further research will be needed to explore techniques that incorporate multispectral information, which can contribute to reducing noise and improving the accuracy of the method.

We wish Dr. Maeda and his team luck for their ongoing efforts towards addressing the remaining issues with this novel method.

Wearable sensors are becoming a promising tool in personalized healthcare and exercise monitoring. In a recent study, researchers from Japan develop a novel wearable chemical sensor capable of measuring the concentration of chloride ions in sweat. By using a heat-transfer printing technique, the proposed sensor can be applied to the outer surface of common textiles to prevent skin irritation and allergies, and could also be useful in the early detection of heat stroke and dehydration.

The remarkable level of miniaturization possible in modern electronics has paved the way for realizing healthcare devices previously confined to the realm of science fiction. Wearable sensors are a prominent example of this. As the name suggests, these devices are worn on the body, usually directly on the skin. They can monitor important bodily parameters, including heart rate, blood pressure, and muscle activity.

Some wearable sensors can also detect chemicals in bodily fluids. For instance, sweat biosensors can measure the concentration of ions in sweat, providing information on their levels in blood. However, designing such chemical sensors is more complex than physical sensors. Direct contact between a wearable chemical sensor and skin can cause irritation and allergies. In contrast, if the sensor is fabricated directly on a wearable textile, its accuracy decreases due to surface irregularities.

In a recent study, a research team, led by Associate Professor Isao Shitanda of the Tokyo University of Science (TUS) in Japan, has developed an innovative sweat biosensor that addresses the aforementioned problems. Their work, published online in ACS Sensors on June 15, 2023, describes the use of a technique called “heat-transfer printing” to fix a thin, flexible chloride ion sensor onto a textile substrate. The study was co-authored by Dr. Masahiro Motosuke, Dr. Tatsunori Suzuki, Dr. Shinya Yanagita, and Dr. Takahiro Mukaimoto of TUS.

“The proposed sensor can be transferred to fiber substrates, and thus can be incorporated into textiles such as T-shirts, wristbands, and insoles,” explains Dr. Shitanda. “Further, health indicators such as chloride ion concentration in sweat can be measured by simply wearing them.”

 

The heat-transfer printing approach offers several advantages. For one thing, the sensor is transferred outside of the piece of clothing, which prevents skin irritation. In addition, the wicking effect of the textile helps spread the sweat evenly between the electrodes of the sensor, creating a stable electrical contact. Moreover, printing the sensor on a flat surface and then transferring it prevents the formation of blurred edges that commonly occur when printing directly onto a textile.

The researchers carefully selected the materials and electrochemical mechanisms of the sensor to avoid risking an allergic reaction for the wearer. After developing the sensor, they conducted various experiments using artificial sweat to verify its accuracy in measuring chloride ion concentration. The change in the electromotive force of the sensor was −59.5 mTV/log CCl−. Additionally, it displayed a Nernst response and a linear relationship with the concentration range of chloride ions in human sweat. Moreover, no other ions or substances typically present in sweat were found to interfere with the measurements.

Lastly, the team tested the sensor on a volunteer who exercised on a static bicycle for 30 minutes, by measuring their perspiration rate, chloride ion levels in blood, and saliva osmolality every five minutes to compare with the data previously gathered by the sensor. The proposed wearable sensor could reliably measure the concentration of chloride ions in sweat.

The sensor can also transmit data wirelessly, making it useful for real-time health monitoring. “Since chloride is the most abundant electrolyte in human sweat, measuring its concentration provides an excellent indicator of the body’s electrolyte balance and a useful tool for the diagnosis and prevention of heat stroke,” remarks Dr. Shitanda.

This research thus demonstrates the potential of using wearable ion sensors for the real-time monitoring of sweat biomarkers, facilitating personalized healthcare development and athlete training management.