FIGURE 3: Long-term cold exposure attenuates HCC development. (A) Representative images of livers from mice exposed to RT (23±1^◦C) or CT (5±1^◦C). White dashed lines highlight regenerative nodules. (B) Percentage of hURI^Hep mice bearing liver tumors. (C-E) Macroscopical characterization of liver tumors, representing (C) percentage of affected area, (D) number of tumors, and (E) tumor size in hURI^Hep mouse livers exposed to RT (23±1^◦C) or CT (5±1^◦C). (F) Representative H&E stainings from liversof hURI^Hep mice exposed to RT or CT. (G-H) Microscopical quantification of the percentage of hURI^Hep mice presenting (G) hepatocytehypertrophy and (H) oval cell hyperplasia, based on liver tissues from (F). (I) Microscopical quantification of the percentage of hURI^Hep mice presenting steatosis based on liver tissues from (F). (J) Representative H&E staining’s from hURI^(KI/KI)Hep mice livers. White arrows highlight oval cell hyperplasia and black arrows highlight anisokaryosis. White dashed lines highlight cholestasis, while the white circle shows a nodule with clear cells. (K) Representative H&E staining’s from hURI^(KI/KI)Hepmice livers highlighting steatosis. White dashed lines highlight hepatocytes with microvesicular steatosis and black arrows show macrovesicular steatosis. (L) Western blot analysis of hURI^Hep mouse livers exposed to RT or CT. Statistical analysis was performed using unpaired two-tailed Student’s t-test. Data are represented as mean ± s.e.m from n independent experiments; *P≤ 0.05, **P ≤ 0.01. Scale bars, 50 µm and 100 µm(F, J,K), and 1 cm (A).