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.

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.

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.