Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment, especially for refractory or relapsed cancers that are resistant to conventional therapies. CAR-T cells are genetically engineered to express CAR molecules on their surface. These CAR-T cells are generated by th e introduction of CAR genes into T cells harvested from a cancer patient. Following the reinfusion of CAR-T cells into the patient, these cells recognize cancer cells by binding to cancer specific antigens to activate CAR signaling and eradicate the cancer cells. However, CAR-T cell therapies face challenges such as CAR-T cell exhaustion and severe toxicities, including on target, off tumor toxicity and cytokine release syndrome. To overcome these hurdles and enhance CAR-T cell performance, fine tuning CAR activation and exhaustion is essential. Optimizing the CAR affinity for its target antigen has proven to be effective to fine tune the CAR-T cell function. This review introduces CAR-T cell therapy, summarizes the current challenges, and explores ongoing efforts to optimize CAR functionality by adjusting the binding affinity.

Not only the importance of the genome sequence as the blueprint of life activity, but also the chemical modification of bases has been clarified to affect various biological phenomena. Chemical modifications of RNA, called epitranscriptome, play an important role in post transcriptional gene regulation. N⁶-metyladenosin (m⁶A), which is the most abundant chemical modification in mRNA, regulates RNA stability, localization, and translation, and is involved in development, differentiation, cancer, and other diseases. Manipulation of m⁶A at specific RNA sequences would open the door to clarify the roles of RNA methylation in various biological phenomena and diseases. The principles and recent progress of molecular tools for RNA sequence-specific m⁶A regulation are outlined here.

Cancer remains the leading cause of death among Japanese people. Preventive treatment before very early-stage cancer becomes malignant, or suppressing recurrence or metastasis, holds potential for a radical cure. Although it is known that so-called "cancer stem cells" produce cancer tissue, their maintenance mechanism remains unclear. We discovered that the intracellular molecule FRS2beta creates the inflammatory microenvironment surrounding very early-stage cancer stem cells, promoting therapeutic resistance and in vivo survival. We also revealed that cancer stem cells constantly create this inflammatory cancer stem cell niche to acquire therapeutic resistance and live in vivo. Furthermore, we successfully isolated a subset of cancer stem cells responsible for cancer recurrence. Our research is expected to contribute to preventing malignant transformation of very early-stage cancer and effectively preventing recurrence and metastasis through targeted therapy of cancer stem cells, ultimately leading to the radical cure of cancer.

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is characterized by TDP-43 aggregates primarily observed in the limbic system regions of the brain, and its frequency increases with age. The LATE neuropathologic changes often coexist with other neurodegenerative diseases, such as Lewy body disease (LBD) and Alzheimer's disease (AD). This study aimed to elucidate the clinicopathological features of LATE, particularly its coexistence with LBD, AD, or their mixed pathologies . The neuropathologic changes of LATE (LATE-NC) in LBD and AD displayed distinct distributional and morphological differences, possibly influenced by Lewy body pathologies and AD pathologies, respectively. Furthermore, LATE-NC was associated with cognitive decline independent of either Lewy or AD neuropathologic changes. These findings emphasize the diversity of LBD and AD and underscore the importance of appropriate patient recruitment in future clinical research.

In September 2021, the Society of Japanese Women Scientists (SJWS) compiled the draft proposal, "To Advance a Research Environment Where Both Women and Men Can Fully Demonstrate Their Abilities in the Era of 100-Years Life ~Free from Barriers of Unconscious Bias~". On the 26th of the same month, the SJWS held a symposium on "Expectations for Female Scientists: Why the Number of Female Scientists is Not Increasing," and finalized the proposal, which was open to the public. This report is a summary by the members who worked on the proposal, including a review of their activities since then, with the aim of disseminating the contents of the proposal to the rest of the world. Since 2005, policies on gender equality have been concrete and steadily promoted, with numerical targets set, but the ratio of female researchers in Japan remains at the lowest level compared to other countries, and ratio of those in higher positions is decreasing further. To solve these issues, it is important to collaborate with foreign countries, as well as to consolidate diverse knowledge and experience, and lead to effective reforms through "convergence of knowledge" and "gendered innovation”. We hope that this report will provide an opportunity to discuss these important issues.

Before its incorporation, the Japanese Society of Women Scientists consisted of a headquarters and branches, with each branch actively engaged in its own activities. After incorporation, due to changes in the organizational structure o f SJWS and management method of the board of directors, the branch's own activities tended to decline. Having served as a Kansai branch director for a long time, I looked back on the changes in my consciousness during my time as a branch director, including my regrets about no t being able to continue independent branch activities.

Even though the spread of COVID 19 has subsided, the use of the web is still effective for regular activities such as board meetings and academic conferences. On the other hand, as new branch s activities, SJWS is expected to play an active role not only in academic fields but also in a variety of fields, such as contributing to local government and supporting human resource networks for women's empowerment.

The 19th International Conference of Women Engineers and Scientists (ICWES19) was held in Auckland, New Zealand, September 3-6, 2023. The total number of participants was 270 (including 50 online participants) from 8 countries, excluding the host country (180 participants). There were four presentations from Japan. Two oral presentations reported on the current situation in Japan with a low gender index and problems such as unconscious bias. One poster presentation was on the SJWS's support and awareness-raising activities for female scientists, and the other was on the Japanese government's support and awareness-raising activities for STEM fields, and on the Japanese children's “turning away from science” and girls' education. The central theme of the conference was “Ensuring STEM diversity and equality,” which had the largest number of presentations, and lively discussions were held on diversity, including gender, and the advancement of women in STEM fields. It was concluded that while there are challenges to women's participation in a traditionally male sector, the situation is showing signs of improvement.

On January 21, 2024, the "New Year Symposium 2024: Reflections on Diversity Promotion in Universities" was held at the Memorial Hall, School of Medicine, Gifu University. The symposium featured keynote speeches by three panelists: Vice President Hiromi Nakano from Toyohashi University of Technology, Vice President Hiroko Tsukamura from Nagoya University, and Vice President Chiho Oyabu from Gifu University. Following the keynote speeches, a comprehensive discussion took place with the participation of facilitators Rika Numano, Director of SJWS from the Tokai Branch (Toyohashi University of Technology), and Maki Koyama, Director of SJWS from the Tokai Branch (Gifu University). The symposium provided insightful reflections on the achievements and challenges of promoting diversity in recent years within three universities. It was a really valuable symposium offering various perspectives for all participants.