Core Viewpoint - The article discusses the "winner effect," a psychological phenomenon where previous victories increase the likelihood of future successes, highlighting gender differences in this effect between male and female mice [2][3]. Group 1: Research Findings - A study by Professor Hu Hailan's team at Zhejiang University revealed that female mice exhibit a weaker "winner effect" compared to male mice, attributed to differences in the excitability of a specific type of inhibitory neuron in the dorsomedial prefrontal cortex (dmPFC) [3][11]. - The research utilized a "tunnel experiment" to establish social hierarchies among mice, confirming that female mice can form stable social ranks, albeit through different behavioral strategies than males [5][10]. - The study demonstrated that activating the dmPFC in female mice could reverse their social standing, indicating that this brain region plays a crucial role in regulating social hierarchy for both sexes [7][8]. Group 2: Neural Mechanisms - The research identified that the excitability of parvalbumin interneurons (PV-IN) in the dmPFC is higher in female mice, leading to a less pronounced "winner effect" due to lower long-term potentiation (LTP) in the neural pathways involved [11][12]. - Experiments showed that enhancing PV-IN excitability in male mice diminished their "winner effect," while inhibiting it in female mice strengthened their "winner effect," confirming the critical role of PV-IN in gender differences [12][14]. Group 3: Evolutionary Perspective - The study suggests that the weaker "winner effect" in female mice may have evolutionary advantages, allowing them to balance competition and cooperation, reduce energy expenditure, and maintain social harmony [16][17]. - This neural mechanism difference reflects adaptive evolution in social roles between males and females, providing insights into how specific neuronal excitability can finely tune social behaviors [17].

Core Insights - The article discusses a study revealing that both gender (male) and smoking are significant risk factors for bladder cancer, influencing the selection and accumulation of specific somatic mutations in normal bladder tissue long before cancer develops [3][9]. Group 1: Molecular Basis of Gender Differences - The study found that male bladder tissue accumulates significantly more driver mutations in key genes (RBM10, CDKN1A, ARID1A) compared to females, indicating a stronger survival or proliferation advantage for cells with these harmful mutations [7]. - This accumulation of "latent" harmful cell clones in males explains the higher risk of bladder cancer in men [7]. Group 2: Impact of Smoking and Aging - The research identified that TERT promoter mutations, common drivers of bladder cancer, can promote the expansion of clones in normal bladder tissue, showing a strong positive correlation with age and smoking history [7]. - Smoking and aging processes directly enhance the growth of potentially carcinogenic clones in normal tissue, significantly increasing cancer risk [7]. Group 3: Research Methodology - The study utilized ultra-deep double-strand DNA sequencing (approximately 5000× depth) to analyze 79 normal bladder samples from 45 individuals, identifying thousands of clone-driving mutations across 16 genes [8]. - This "Natural Saturation Mutagenesis" approach allows for a more accurate reflection of human biology compared to traditional cell line or animal model experiments, providing insights into precancerous lesions in various tissues [8]. Group 4: Implications for Cancer Risk and Prevention - The findings challenge the traditional dichotomy of "health" and "disease," showing that cancer risk factors like male gender and smoking begin shaping normal tissue cell clone landscapes years before cancer onset [9]. - The study offers new molecular targets and theoretical foundations for high-risk population screening and early intervention for bladder cancer [9].