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As artificial intelligence (AI) technology is introduced into different areas of society, understanding people’s willingness to accept AI decisions emerges as a critical scientific and societal issue. It is an open question whether people can accept the judgement of humans or AI in situations where they are unsure of their judgement, as in the trolley problem. Here, we focus on justified defection (non-cooperation with a bad person) in indirect reciprocity because it has been shown that people avoid judging justified defection as good or bad. We explore which decisions people would accept when AI and humans make different decisions in the justified defection. Two experiments revealed that only when AI judged positively and a human judged negatively, people rated the AI’s judgement as better. The research suggests that people’s acceptance of AI decisions depends on estimating the hidden intentions behind societal norms. It offers new insights into human norm analysis by examining the differences in acceptance between AI and human judgments.

In recent years, considerable research and development efforts are devoted to improving the performance of polymer electrolyte fuel cells. However, the power density and catalytic activities of these energy conversion devices are still far from being satisfactory for large-scale operation. Here we report performance enhancement via incorporation, in the cathode catalyst layers, of a ring-structured backbone matrix into ionomers. Electrochemical characterizations of single cells and microelectrodes reveal that high power density is obtained using an ionomer with high oxygen solubility. The high solubility allows oxygen to permeate the ionomer/catalyst interface and react with protons and electrons on the catalyst surfaces. Furthermore, characterizations of single cells and single-crystal surfaces reveal that the oxygen reduction reaction activity is enhanced owing to the mitigation of catalyst poisoning by sulfonate anion groups. Molecular dynamics simulations indicate that both the high permeation and poisoning mitigation are due to the suppression of densely layered folding of polymer backbones near the catalyst surfaces by the incorporated ring-structured matrix. These experimental and theoretical observations demonstrate that ionomer’s tailored molecular design promotes local oxygen transport and catalytic reactions. Polymer electrolyte fuel cells are promising but suffer from low performance. Here, the authors use a combination of electrochemical measurements and molecular dynamics simulations to reveal the role of the highly oxygen permeable ionomer in polymer electrolyte fuel cells that enhances the oxygen transport and catalytic activity.

Humans have achieved widespread cooperation, largely sustained by mechanisms such as indirect reciprocity, which relies on reputation and social norms. People are highly motivated to maintain a good reputation, and social norms play a critical role in reputation systems by defining acceptable behavior, helping prevent exploitation by free-riders. However, there is a gap between theory and experiment in handling reputation information, with experiments often failing to capture the complexity that theoretical models propose. Here, we address two key issues: what kind of information is needed to define reputation as a social norm and the appropriate level of granularity required for reputation information to function effectively. This paper combines scenario-based experiments and evolutionary game theory to investigate the social norms individuals adopt in real-world settings, aiming to uncover the stability of these norms. Our results show that reputations should be categorized into three levels good, neutral, and bad. Results suggest gradual reputation dynamics that increase and decrease gradually due to cooperation or defection. However, a person’s reputation remains unchanged only when they defect against a bad reputation. Our experimental and theoretical results support critical insights into the dynamics of reputation and social norms within indirect reciprocity, challenging traditional binary reputational evaluations. The gradual nature of reputation updating and the use of nuanced evaluations provide a more realistic model of reputation dynamics.

Cytosine base editing enables the installation of specific point mutations without double-strand breaks in DNA and is advantageous for various applications such as gene therapy, but further reduction of off-target risk and development of efficient delivery methods are desired. Here we show structure-based rational engineering of the cytosine base editing system Target-AID to minimize its off-target effect and molecular size. By intensive and careful truncation, DNA-binding domain of its deaminase PmCDA1 is eliminated and additional mutations are introduced to restore enzyme function. The resulting tCDA1EQ is effective in N-terminal fusion (AID-2S) or inlaid architecture (AID-3S) with Cas9, showing minimized RNA-mediated editing and gRNA-dependent/independent DNA off-targets, as assessed in human cells. Combining with the smaller Cas9 ortholog system (SaCas9), a cytosine base editing system is created that is within the size limit of AAV vector. Base editing is promising for gene therapy, but in vivo delivery has been limiting. Here the authors perform structure-based rational engineering of the cytosine base editing system Target-AID to minimise off-target effects and decrease its size.

Human cooperation relies on both direct and indirect reciprocity. While these mechanisms are often treated as separate, real-world decision-making frequently involves integrating the two. However, the existing literature has paid limited attention to the contextual factors and mechanisms supporting the coexistence of direct and indirect reciprocity. This study proposes and analyses a model of integrated reciprocity that combines personal experiences with reputational information. Using agent-based simulations, we systematically and comprehensively evaluate social norms and demonstrate that tolerant integrated reciprocity, which incorporates a partner’s past behaviour and reputation, can sustain cooperation more robustly than strategies based solely on direct or indirect reciprocity. In particular, the combination of tolerant integrated reciprocity with the “Standing” norm maintains high cooperation levels even in noisy environments characterised by assessment and implementation errors. These findings suggest that tolerance and using multiple information sources provide an adaptive advantage in sustaining cooperation.

Indirect reciprocity is one of the major mechanisms in the evolution of human cooperation. In indirect reciprocity, social norms with which individuals distinguish good people from bad people play essential roles. Despite extensive studies on the evolution of cooperation in indirect reciprocity, little is known about which social norms people actually adopt. Here we reveal what kind of norms are adopted by people in indirect reciprocal situations in daily life by using scenario-based experiments. The results showed that people evaluated \"justified defection\" as neither good nor bad and withheld their evaluation. Theoretically, social norms that evaluate justified defection as good are required for cooperation to be stable. However, the norm that people actually adopted deviates from the theoretical predictions. Our results indicate the necessity to reconsider the justification of \"justified defection\" in the evolution of cooperation.

Over-expression of transmembrane serine protease 4 (TMPRSS4), which promotes epithelial-to-mesenchymal transition and cancer cell invasion, is associated with poor prognosis in patients with gastric cancer. This study aimed to develop a new anti-TMPRSS4 small interfering RNA (siRNA) therapeutic strategy by engineering lipid nanoparticles (LNPs). The biodistribution and anti-tumor effect of anti-TMPRSS4-siRNA loaded LNPs were evaluated in vitro and in vivo in mice with gastric cancer tumors (subcutaneous xenograft NUGC-3 cell tumors). LNPs demonstrated enhanced accumulation in the tumor compared with naked siRNA. A significant reduction in gastric cancer tumor growth was observed in mice undergoing combination therapy with LNPs and fluorouracil (5-FU) compared to mice receiving 5-FU alone. Anti-TMPRSS4-siRNA loaded LNPs may be considered a promising therapeutic modality for gastric cancer.

With increasing concern over online misinformation in perspective, this study experimentally examined the cognitive as well as the affective consequences of online search. Results of the two experiments using widely shared, prejudiced misinformation about an ethnic minority in Japan indicated that (a) online search reduces on average the likelihood of believing the misinformation, (b) the magnitude of the effect is larger among those who are predisposed to believe the misinformation, (c) cognitive correction is observed whether searchers are motivated to achieve a directional goal or an accuracy goal, and (d) online search deteriorates affective feeling toward the target groups of the misinformation. Theoretical implications are discussed in relation to the robustness of confirmation bias in online search and the “belief echo” in which exposure to negative misinformation continues to shape attitudes even after the misinformation has been effectively discredited.

Sperm–egg fusion is indispensable for completing mammalian fertilization. Although the underlying molecular mechanisms are poorly understood, requirement of two spermatozoon factors, IZUMO1 and SPACA6, and two oocyte factors, CD9 and the IZUMO1 counter-receptor JUNO, has been proven by gene disruption, and the binding of cells to an oocyte can be reconstituted by ectopic expression of IZUMO1. Here we demonstrate that robust IZUMO1-dependent adhesion of sperm with an oocyte accompanies the dimerization of IZUMO1. Despite the intrinsic dimeric property of its N-terminal region, IZUMO1 is monomeric in spermatozoa. Interestingly, JUNO associates with monomeric IZUMO1, which is then quickly removed as tight adhesion of the two cells is subsequently established. We therefore propose that global structural rearrangement of IZUMO1 occurs on JUNO recognition and that this rearrangement may then initiate force generation to overcome repulsion between the juxtaposing membranes, through an unidentified receptor on the egg. Sperm-egg fusion is facilitated by the sperm-specific receptor IZUMO1 and the egg-specific counter-receptor JUNO. Here Inoue et al. show that JUNO first binds to monomeric IZUMO1; IZUMO1 then dimerizes and excludes JUNO from the sperm-egg interface, suggesting the existence of a IZUMO1 dimer receptor.

Detection of mechanical stress is essential for diverse biological functions including touch, audition, and maintenance of vascular myogenic tone. PIEZO1, a mechano-sensing cation channel, is widely expressed in neuronal and non-neuronal cells and is expected to be involved in important biological functions. Here, we examined the possibility that PIEZO1 is involved in the regulation of synovial sarcoma cell-viability. Application of a PIEZO1 agonist Yoda1 effectively induced Ca2+ response and cation channel currents in PIEZO1-expressing HEK (HEK-Piezo1) cells and synovial sarcoma SW982 (SW982) cells. Mechanical stress, as well as Yoda1, induced the activity of an identical channel of conductance with 21.6 pS in HEK-Piezo1 cells. In contrast, Yoda1 up to 10 μM had no effects on membrane currents in HEK cells without transfecting PIEZO1. A knockdown of PIEZO1 with siRNA in SW982 cells abolished Yoda1-induced Ca2+ response and significantly reduced cell cell-viability. Because PIEZO1 is highly expressed in SW982 cells and its knockdown affects cell-viability, this gene is a potential target against synovial sarcoma.