Japan’s NARO develops new apple tree variety suitable for automatic harvesting Japan’s National Agricultural Research Organization NARO has developed a new apple variety that has compact fruit tree branches that do not spread out horizontally. It has been named “Benitsurugi.” The apple trees can be planted close together and the movement during harvesting can be simplified, making it suitable for automatic harvesting. Although the coloring is inferior to existing varieties, the taste is said to be high in sugar content and has an excellent balance of sugar and acid. “Benitsurugi” was created by crossbreeding a variety that inherits the compact tree shape of the overseas apple variety “Wijcik” with the domestic varieties “Fuji” and “Sansa”. NARO is currently in the process of registering the variety “Benitsurugi”, and will begin providing seedlings after the procedure is completed, which usually takes about one to two years.

Germ cells may regulate aging in vertebrates A research team at Osaka University has uncovered the mechanism by which females live longer than males. They found that the reproductive cells of both males and females control their lifespan, and that eggs have a molecular mechanism that leads to longer lifespans which is not available to sperm cells. The research team around Professor Futoshi Ishitani at the Institute for Microbial Diseases, Osaka University used the turquoise killifish in their experiments. Turquoise killifish have a short lifespan of just a few months, with males living shorter than females, and they also undergo a similar aging process to humans. When during embryo development, antisense nucleic acid against the dnd gene was administered to remove the germ cells, the lifespan of males and females was almost the same, with females living even shorter and males living longer than normal, suggesting that germ cells were responsible for the longer lifespan in females. To identify the molecular mechanism , Professor Ishitani and his team examined the endocrine system of turquoise killifish. They found that females had a decreased level of estrogen, which was accompanied by an increase in lipid synthesis and an increase in blood clotting factors, increasing the risk of cardiovascular disease. They also found that insulin/insulin-like growth factor signaling, which controls body growth, was activated, increasing damage such as oxidative stress. They concluded that in females, eggs may suppress aging by releasing estrogen signals and suppressing insulin/IGF signals. On the other hand, males from which germ cells had been removed showed increased muscle regeneration ability, skin collagen content, and bone mass, all of which normally decrease with age. Gene expression of the Cyp2r1 enzyme, which converts vitamin D into its active form, was increased, and vitamin D signaling was activated in the muscles and skin, suggesting that vitamin D signaling suppressed aging throughout the body. When vitamin D was administered to normal turquoise killifish, it was found to have an effect of extending the lifespan of both males and females, although there were differences in the effect between the sexes. Vitamin D functioned as an anti-aging hormone. There have been cases in which genetic polymorphisms that may promote vitamin D signaling have been found in long-lived humans, so it is expected that vitamin D may also contribute to human longevity. However, administering excessive amounts to turquoise killifish does not enhance the effect, and it is known that excessive intake in humans and mice can cause health problems, so it is necessary to consider the appropriate amount.

Green Earth Institute completes pilot plant in Kanto Biofoundry Center, shortens scale-up NEDO and Green Earth Institute, Inc. (GEI) are currently verifying the functionality of the Kanto Biofoundry Center, which was completed in Mobara City, Chiba Prefecture, as part of the “Development of Bio-based Product Production Technology to Accelerate the Realization of Carbon Recycling” . Thanks to the Center’s know-how in experimental design and production systems using scale-down models and CFD analysis, the Center has succeeded in completing the scale-up consideration period for projects that were previously thought to take about three years in about six months, which is about one-sixth of the conventional period. In the future, the Center will aim to expand the bioeconomy through material production systems that utilize microorganisms in a wide range of fields, and will increase its demonstration experience with various production materials, including other microbial species such as filamentous fungi, in addition to E. coli and yeast, which have a proven track record. The base can conduct scale-up considerations using fermentation tanks from 0.25 L to a maximum of 3,000 L. In order to significantly reduce the time and cost required for gradual scale-up, we are working on developing technologies for production systems in scale-down models, new pretreatment methods, and systems that calculate costs and CO2 emissions that can be implemented simply and timely, using know-how in experimental design and CFD analysis that simulates the conditions inside fermentation tanks, and we will apply these technologies to scale-up cases that are adopted as demonstration cases. The new equipment is fully operational in June 2023, and wewill be working on substance production demonstrations using microbial functions in accordance with the implementation plan until the end of this project in fiscal 2026, and in fiscal 2023, scale-up will be done in four cases, with different chemical products such as amino acids, peptides, oils and enzymes being produced.

2024/05 Pharma Foods succeeds to prepare fiber materials from eggshell membranes 2.63 million tons of chicken eggs are used annually in Japan, and about half are sold as raw eggs for home use, while the remaining half are used as liquid eggs for commercial use. During the manufacturing process of liquid eggs, am estimated amount of 260,000 t of eggshells and 10,000 t of eggshell membranes are produced as waste. The eggshells produced during the liquid egg manufacturing process will rot if left unattended Their main component is calcium carbonate.The eggshell membrane is a protein complex containing collagen and cystine, which has the function of not allowing water to pass through but allowing oxygen to take in, and has antibacterial and anti-inflammatory effects to protect fertilized egg cells. The company is already using it as an ingredient in health foods. The company has developed fibers made by spinning a 1:9 mixture of hydrolyzed and dissolved eggshell membranes and regenerated cellulose fibers. It is named ovoveil and currently studied with textile manufacturers to develop its application. Eggshell membranes have the advantage of being concentrated in liquid egg manufacturing factories. They could bs used to produce 100,000 tons of fiber which would fully meet the needs of the apparel industry. The global annual production of sheep wool is 1 million tons, and cashmere from cashmere goats, is  20,000 tons a year. At present, it is recommended that Obovere be added to approximately 30% of the final product. For example, when making T-shirts, the blend is 70% cotton and 30% obovere. Oboveil has a lot of cystine, which is relatively similar to keratin, so physical properties are similar to animal fibers. Textile manufacturers have already praised its good texture,” Koga said. The deputy director reveals. We also evaluated its functionality and confirmed that it improved the skin’s barrier function, measured by the amount of water evaporated from the skin, and kept the skin slightly acidic. With the support of the New Energy and Industrial Technology Development Organization (NEDO),  the development of next-generation production technology for Ovoveil contains 30% eggshell membranes while utilizing enzymes. We will develop energy storage devices that take advantage of the electrical properties of hydrolyzed eggshell membranes, and develop agricultural fertilizers using eggshell membranes. The company has so far confirmed that eggshell membrane hydrolyzate can be made into nanofibers and used as a power storage device.

Making rainbow trout give birth to salmon A research team led by Professor Goro Yoshizaki at the Tokyo University of Marine Science and Technology has  succeeded in laying salmon eggs in rainbow trout using a surrogate broodstock technique that involves transplanting reproductive stem cells between different species. It is based on the observation that when a cell population containing germline stem cells is extracted from a live fish or a recently deceased fish (donor fish) and placed into the abdominal cavity of a host fish, the germline stem cells are not rejected by the immune system and migrate to the gonads, engraft, and mature. Professor Yoshizaki is aiming for applied research using this technology, such as making mackerel lay bluefin tuna eggs and increasing the number of seedlings. So far, he has succeeded in making rainbow trout give birth to yamame trout and char, and in making Kusafugu give birth to tiger puffer fish. King salmon are in high demand for food, but the problem with aquaculture is that it takes three to seven years for the parent fish to reach sexual maturity, and they only spawn once. This research might make it possible to repeatedly produce king salmon eggs and sperm using rainbow trout host fish, and to produce seedlings while reducing the cost of raising king salmon broodstock.

NEDO’s Energy Saving and Non-Fossil Energy Conversion Technology Strategy 2024 NEDO and the Agency for Natural Resources and Energy of the Ministry of Economy, Trade and Industry have identified important technologies that will significantly contribute to energy conservation and non-fossil energy conversion in the future. In order to effectively promote the research, development and dissemination of energy conservation technology and non-fossil energy conversion technology, they have formulated the “Energy Saving and Non-Fossil Energy Conversion Technology Strategy 2024. This strategy includes the “Sixth Energy Basic Plan,” “Green Growth Strategy to Achieve Carbon Neutrality in 2050,” “Clean Energy Strategy Interim Review,” “Basic Policy for Realizing GX,” and “Rationalization of Energy Use. In light of the amendments to the Act on Conversion to Non-Fossil Energy they have newly added and compiled technologies related to conversion to non-fossil energy that will lead to decarbonization. The publication contains images related to important technologies stipulated in the “Energy Conservation and Non-Fossil Energy Conversion Technology Strategy 2024”

IQVIA: Japan’s pharmaceutical market 2023 According to a market survey by ISQIA,”anti-tumor drugs” ranked first at 1,959.4 billion yen. The market is overwhelmingly large and continues to grow strongly, approaching 2 trillion yen. Its share of the total market was 17.2%. IQVIA said that in addition to Imfinzi, the anti-CD79b monoclonal antibody conjugated to a microtubule inhibitor, Polivee (polatuzumab vedotin, Chugai Pharmaceutical Co., Ltd.), contributed to growth in this area with sales increasing 81.4% year-on-year. IQVIA predicts that growth will continue, centered on new drugs, and that it will exceed 2 trillion yen in 2024. The second-largest “diabetes treatment” market increased by 7.1% compared to the previous year, and growth accelerated. “Sales of SGLT-2 inhibitors increased due to the addition of an indication for chronic kidney disease (CKD), as well as GLP-1 receptor agonists Ozempic (semaglutide, Novo Nordisk) and Libersus ( Significant growth in sales of semaglutide (MSD) also contributed.” (IQVIA) In third place was the immunosuppressant market, with rheumatoid arthritis treatment drug Rinvoc (upadacitinib, AbbVie) increasing 71.2% year-on-year, and atopic dermatitis treatment drug Dupixent (dupilumab, Sanofi) increasing by 71.2% compared to the previous year. This was a significant increase of 37.6%. “Dupixent’s expanded use in children contributed to its growth” (IQVIA). Due to the transition of COVID-19 to a Class 5 infectious disease in May 2023, sales of diagnostic test reagents decreased significantly by 20.8% compared to the previous year, dropping two ranks to 6th place. On the other hand, systemic antiviral drugs, which include therapeutic drugs, rose from 6th place in the previous year to 4th place. Due to the expansion of the market for COVID-19 treatment drugs and growth in influenza treatment drugs, sales recorded high growth of 48.6% year on year. Additionally, renin-angiotensin system agonists, which had always been ranked within the top 10 since the top-line announcement began in 2005, finally dropped out of the rankings this quarter. Chugai Pharmaceutical tops corporate sales ranking for third consecutive year. Sales were 539.9 billion yen, an increase of 1.4% from the previous year. Growth in Polibee and strong sales of the main product Hemlibra (emicizumab), a treatment for hemophilia A, contributed. AstraZeneca, which ranked third in the previous year, emerged in second place, with sales of 513.2 billion yen, an increase of 12.6% compared to the previous year. In addition to Imfinzi, the diabetes drug Farxiga (dapagliflozin) grew. Sales of Farxiga continue to grow due to expanded indications for chronic heart failure and chronic kidney disease. Third place was MSD, with sales of 497.2 billion yen, an increase of 30.2% from the previous year, showing the highest growth rate among the top 20 companies. In addition to the aforementioned Lagebryo and Keytruda, the HPV vaccine Sylgard 9 (recombinant precipitated 9-valent human papillomavirus-like particle vaccine [yeast-derived]) contributed to growth. IQVIA Japan classifies the domestic medical drug market into three markets: “hospitals,” “practitioners,” and “pharmacies and others.” In fiscal 2023, sales in the hospital market will increase by 4.6% from the previous year to 5,330.6 billion yen, in the private practice market by 2.0% to 2,114.9 billion yen, and in pharmacies and other sales by 3.3% to 3,925.2 billion yen. became.  

Human vaccination with micro algae vaccines? Professor Shinya Miyagijima of the National Institute of Genetics and colleagues have established a new haploid cell line from the microalgae Cyanidium calgarum discovered in acidic hot springs in Japan. The established haploid strain does not have a cell wall. Therefore, it is easy to perform genetic recombination. There is no need to disrupt cell walls during protein extraction, reducing extraction and purification costs. In addition, since it grows in a strongly acidic environment, it is difficult for other microorganisms to contaminate it, making it easy to cultivate aseptically. Furthermore, because it is haploid, it is genetically stable and can be stored for long periods at room temperature. Professor Miyagijima and his colleagues have also established technology for culturing haploid Ideyukogome at high density and for high expression of heterologous genes, and collaborate to develop an oral vaccine. When administering vaccines orally, the acid-resistant microalgae protect the antigenic proteins  and will be released in the neutral or hypotonic environment of the intestinal tract. In order to use it as an oral vaccine platform, the researchers have made various improvements using genetic recombination technology and, using green fluorescent protein (GFP) have shown that most of GFP reached the small intestine rather than the stomach. They also expressed a protein in which an epitope recognized by intestinal M cells was added to the envelope protein of the rabies virus, in order to investigate whether immunity could be induced by orally administering Cyanidium calgarum into which an antigen protein had been introduced. It was confirmed that blood IgG could be induced via the intestinal tract. Based on this prior research, this project aims to develop oral vaccines for Japanese encephalitis virus and enterovirus, and to obtain non-clinical proof of concept (POC) by March 2025. If this concept can be made into oral medicine, it will be possible to administer vaccines without needles or syringes. The labor required for vaccination can also be reduced. Furthermore, if a cold chain is not required for transportation or manufacturing, vaccines can be distributed throughout the world. Further plans are to feed the dried powder to mice to evaluate whether it is effective. If the dry powder functions as a vaccine, it would have major advantages in terms of storage and transportation.

2024/04 Mitsui Chemicals starts producing chemicals from pyrolyzed bio & waste plastic oil, and cooperates with Kao on polymer recycling Mitsui Chemicals has started to use pyrolyzed oil (hereinafter referred to as waste plastic decomposed oil) procured from CFP Co. in its cracker at Osaka factory (Takaishi City, Osaka Prefecture) for mass production of a wide range of products (chemicals and plastics). Waste plastic cracked oil (“RePlayer”), like petroleum-derived naphtha and biomass naphtha (“BePlayer”), is a hydrocarbon oil, and by feeding it into a cracker, basic raw materials such as ethylene, propylene, C4 and C5 fractions, and benzene are produced. Since basic chemicals such as phenol and plastics such as polyethylene and polypropylene are manufactured from the obtained basic raw materials, the physical properties of derivative products (chemicals and plastics) are equivalent to existing products (virgin products). The relative contents of bio and recycled raw materials in these products will be determined using the mass balance method. In addition, waste plastics produced by Kao Corporation will be used as raw materials in a joint study to implement a circular scheme through chemical recycling to manufacture recycled plastic and use it in Kao products.

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