Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

Eight-week-old male C57BL/6 mice were purchased from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Sorafenib (10 mg/kg, once every other day) was suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. The livers were collected 2 weeks after surgery under general anesthesia.

ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports.

After a one-week acclimatization period, rats were randomly divided into four experimental groups of six rats each. Group I (the control group) received saline intraperitoneally in the same manner as BLM injections, as well as 1% carboxymethyl cellulose (CMC) orally in the same manner as EMPA. Group II (the BLM-treated group) received BLM (15 mg/kg) intraperitoneally three times per week for four successive weeks in order to induce pulmonary fibrosis. Group III (the EMPA-treated group) received EMPA dissolved in 1% CMC orally via oral gavage at a dose of 10 mg/kg/day throughout the experimental period. Group IV (the combined EMPA and BLM-treated group) received EMPA (10 mg/kg) orally via oral gavage seven days before BLM administration and continued for four weeks after BLM injection.

6-8-week-old, 20 ± 2 g, male ICR mice, obtained from Nanjing Medical University (Nanjing, China), were randomly divided into five groups (n = 8 per group). Mouse model of chronic liver fibrosis was established by 10% carbon tetrachloride (CCl4, 0.5 ml/100 g body weight) injection. Groups are follows: (1) Control group was intraperitoneally (i.p.) injected with olive oil; (2) Model group was i.p. injected with 10% CCl4 every other day a week for 8 weeks; (3) Low-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 50 mg/kg artesunate for last 4 weeks; (4) Middle-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 100 mg/kg artesunate for last 4 weeks; (5) High-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 200 mg/kg artesunate for last 4 weeks.

6-week-old male mice (20-25 g) were randomly allocated to the indicated groups and housed in cages with ad libitum access to food and water, following habituation to a 12 h light/dark cycle. The experimenter was blinded to the group allocation. The mouse liver fibrosis model group was established via intraperitoneal (i.p.) injection with TAA or carbon tetrachloride (CCl4) for 6 weeks. The control group was injected i.p. with the same volume of olive oil or saline only. For the BBR group, a dose of BBR (200 mg/kg/day) was given by oral gavage. In addition to the i.p. injection. with TAA or CCl4, the mice in the treatment group received BBR intragastrically. In the inhibitor group, besides the injected i.p. with TAA and BBR oral gavage treatment, mice were injected i.p. with a dose of Fer-1 (1 mg/kg/day). Mice were sacrificed under 3% isoflurane anesthesia after 6 weeks of treatment; blood and liver tissue samples were taken and processed for subsequent analyses. At least five mouse hepatic sections were utilized in every group.

Male C57BL/6 mice (6-8-weeks old; Vitalriver, Beijing, China) were employed. Briefly, 200 ul AAV8-HBV-1.2 was introduced through the tail vein. The exosomes (10 ug) derived from HBV-infected LO2 cells were dissolved in PBS (50 ul) and introduced through the tail vein 2 h after AAV8-HBV-1.2 injection. Mice were anesthetized by inhalation with 3% isoflurane and sacrificed by cervical dislocation after 4 weeks to collect livers for hematoxylin-eosin (HE) and Masson's Trichrome staining and measurement of liver injury as previously described.

Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously.

Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously.

The animal experiment scheme was approved by the institution of Nanjing University ofChinese Medicine (Nanjing, China) and the local animal protection and utilization committee. After the last administration, diet was prohibited, but drinking water was not restricted. 24 h later, the mice were weighed and taken blood.

ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports.

A total of 24 C57BL/6 mice were obtained from the Sippr-BK laboratory animal Co., Ltd. (Shanghai, China). They were randomly divided into four groups: Group I, Vehicle (control); Group II, CCl4; Group III, CCL4 + Vector; Group IV, CCL4 + oeTRIM26. Liver fibrosis was induced in Groups II - IV, by intraperitoneally injecting 50% carbon tetrachloride (CCl4) in corn oil (0.1 mL/100 g body weight) over 8 weeks (3 times/week); control mice were injected with corn oil only. Then, recombinant adenovirus Vector or oeTRIM26 (5 x 10⁹ pfu/mouse, 0.5 mL) was injected into the mice of Group III or IV, respectively, through the tail vein.

ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports.