Pub Date : 2026-01-19DOI: 10.1016/j.freeradbiomed.2026.01.027
Hao Xu , Jingyi Yang , Yu Zhang , Shihui Li , Ziwei Wang , Xiaojin Li , Mixia Cao , Erhui Jin , Shenghe Li , Chang Liu , Lei Li
Cadmium (Cd), a pervasive environmental toxicant, induces hepatotoxicity via mitochondrial damage and dysregulated inflammation. Astragaloside IV (AS-IV), the primary bioactive constituent of Astragalus membranaceus with antioxidative/anti-inflammatory properties, has an undefined regulatory role in the cGAS-STING axis during Cd-induced hepatic injury. In this study, the cytoprotective mechanisms of AS-IV against Cd-induced hepatotoxicity were investigated. The results showed that Cd exposure significantly impaired hepatocellular viability, induced mitochondrial dysfunction, promoted mitochondrial DNA (mtDNA) release into the cytosol, and thereby activated the cGAS-STING signaling pathway, while AS-IV intervention effectively mitigated Cd-induced mitochondrial perturbations, suppressed mtDNA efflux, and inhibited cGAS-STING pathway activation by attenuating mtDNA-dependent STING activation via suppressing cytosolic mtDNA release.
Collectively, AS-IV exerts robust hepatoprotection against Cd toxicity via preservation of mitochondrial integrity, inhibition of cytosolic mtDNA translocation, and suppression of cGAS-STING-driven innate immune hyperactivation. These findings nominate AS-IV as a viable therapeutic countermeasure against heavy metal-induced organ damage.
镉（Cd）是一种普遍存在的环境毒物，通过线粒体损伤和炎症失调引起肝毒性。黄芪甲苷（Astragaloside IV, AS-IV）是黄芪的主要生物活性成分，具有抗氧化/抗炎作用，在cd诱导的肝损伤过程中对cGAS-STING轴的调节作用尚未明确。本研究探讨了AS-IV对cd诱导的肝毒性的细胞保护机制。结果表明，Cd暴露显著损害肝细胞活力，诱导线粒体功能障碍，促进线粒体DNA （mtDNA）释放到细胞质中，从而激活cGAS-STING信号通路，而AS-IV干预通过抑制细胞质mtDNA释放来减弱mtDNA依赖性的STING激活，从而有效减轻Cd诱导的线粒体扰动，抑制mtDNA外泄，抑制cGAS-STING通路激活。总的来说，AS-IV通过保存线粒体完整性、抑制细胞质mtDNA易位和抑制cgas - sting驱动的先天免疫过度激活，对Cd毒性具有强大的肝保护作用。这些发现表明as - iv是一种可行的治疗重金属引起的器官损伤的对策。
{"title":"Targeting mitochondrial permeability and cytosolic mtDNA release: Astragaloside IV suppresses cGAS-STING signaling pathway to protect against cadmium-induced hepatotoxicity","authors":"Hao Xu , Jingyi Yang , Yu Zhang , Shihui Li , Ziwei Wang , Xiaojin Li , Mixia Cao , Erhui Jin , Shenghe Li , Chang Liu , Lei Li","doi":"10.1016/j.freeradbiomed.2026.01.027","DOIUrl":"10.1016/j.freeradbiomed.2026.01.027","url":null,"abstract":"<div><div>Cadmium (Cd), a pervasive environmental toxicant, induces hepatotoxicity via mitochondrial damage and dysregulated inflammation. Astragaloside IV (AS-IV), the primary bioactive constituent of <em>Astragalus membranaceus</em> with antioxidative/anti-inflammatory properties, has an undefined regulatory role in the cGAS-STING axis during Cd-induced hepatic injury. In this study, the cytoprotective mechanisms of AS-IV against Cd-induced hepatotoxicity were investigated. The results showed that Cd exposure significantly impaired hepatocellular viability, induced mitochondrial dysfunction, promoted mitochondrial DNA (mtDNA) release into the cytosol, and thereby activated the cGAS-STING signaling pathway, while AS-IV intervention effectively mitigated Cd-induced mitochondrial perturbations, suppressed mtDNA efflux, and inhibited cGAS-STING pathway activation by attenuating mtDNA-dependent STING activation via suppressing cytosolic mtDNA release.</div><div>Collectively, AS-IV exerts robust hepatoprotection against Cd toxicity via preservation of mitochondrial integrity, inhibition of cytosolic mtDNA translocation, and suppression of cGAS-STING-driven innate immune hyperactivation. These findings nominate AS-IV as a viable therapeutic countermeasure against heavy metal-induced organ damage.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 239-251"},"PeriodicalIF":8.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.freeradbiomed.2026.01.024
Yang Yu , Zhangyu Liu , Jiayu Huang , Xun Qin , Xi Chen , Huiling Nie , Jin Yao , Juxue Li , Qin Jiang
Background
Pathological ocular neovascularization is closely linked to aberrant histone modifications, yet the underlying molecular mechanisms remain incompletely defined. This study investigates the role of the histone demethylase JMJD1C and its encoding gene Jmjd1c in driving pathological angiogenesis and evaluates its therapeutic potential in ocular proliferative vascular diseases.
Methods
Jmjd1c expression was examined in mouse models of ocular neovascularization and in endothelial cells (ECs) using immunostaining, qRT-PCR, and Western blotting. The pro-angiogenic functions of JMJD1C were assessed through EdU incorporation, Transwell migration, tube-formation, and spheroid-sprouting assays in vitro, as well as retinal flat-mount isolectin-B4 staining and H&E staining in vivo. RNA sequencing, immunostaining, qPCR, Western blotting, and ChIP-qPCR were employed to dissect the molecular mechanisms by which JMJD1C regulates pathological angiogenesis.
Results
Endothelial-specific deletion of Jmjd1c markedly reduced pathological neovascularization in both oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. Loss of JMJD1C impaired endothelial cell proliferation, migration, tube formation, and sprouting angiogenesis. Mechanistically, Jmjd1c deletion suppressed Srebf2 transcription and cholesterol biosynthesis by increasing repressive H3K9me2 histone marks in endothelial cells. Pharmacological inhibition of JMJD1C similarly attenuated neovascularization in wild-type mice.
Conclusions
JMJD1C acts as a key regulator of pathological ocular angiogenesis through histone demethylation-mediated control of endothelial cholesterol biosynthesis. These findings establish JMJD1C and the Jmjd1c–Srebf2 regulatory axis as promising therapeutic targets for ocular vascular diseases.
{"title":"Endothelial JMJD1C drives pathological ocular neovascularization by activating SREBF2-dependent cholesterol biosynthesis","authors":"Yang Yu , Zhangyu Liu , Jiayu Huang , Xun Qin , Xi Chen , Huiling Nie , Jin Yao , Juxue Li , Qin Jiang","doi":"10.1016/j.freeradbiomed.2026.01.024","DOIUrl":"10.1016/j.freeradbiomed.2026.01.024","url":null,"abstract":"<div><h3>Background</h3><div>Pathological ocular neovascularization is closely linked to aberrant histone modifications, yet the underlying molecular mechanisms remain incompletely defined. This study investigates the role of the histone demethylase JMJD1C and its encoding gene <em>Jmjd1c</em> in driving pathological angiogenesis and evaluates its therapeutic potential in ocular proliferative vascular diseases.</div></div><div><h3>Methods</h3><div><em>Jmjd1c</em> expression was examined in mouse models of ocular neovascularization and in endothelial cells (ECs) using immunostaining, qRT-PCR, and Western blotting. The pro-angiogenic functions of JMJD1C were assessed through EdU incorporation, Transwell migration, tube-formation, and spheroid-sprouting assays in vitro, as well as retinal flat-mount isolectin-B4 staining and H&E staining in vivo. RNA sequencing, immunostaining, qPCR, Western blotting, and ChIP-qPCR were employed to dissect the molecular mechanisms by which JMJD1C regulates pathological angiogenesis.</div></div><div><h3>Results</h3><div>Endothelial-specific deletion of <em>Jmjd1c</em> markedly reduced pathological neovascularization in both oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. Loss of JMJD1C impaired endothelial cell proliferation, migration, tube formation, and sprouting angiogenesis. Mechanistically, <em>Jmjd1c</em> deletion suppressed <em>Srebf2</em> transcription and cholesterol biosynthesis by increasing repressive H3K9me2 histone marks in endothelial cells. Pharmacological inhibition of JMJD1C similarly attenuated neovascularization in wild-type mice.</div></div><div><h3>Conclusions</h3><div>JMJD1C acts as a key regulator of pathological ocular angiogenesis through histone demethylation-mediated control of endothelial cholesterol biosynthesis. These findings establish JMJD1C and the <em>Jmjd1c</em>–<em>Srebf2</em> regulatory axis as promising therapeutic targets for ocular vascular diseases.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 181-195"},"PeriodicalIF":8.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.freeradbiomed.2026.01.025
Zeyu Tang , Chen Li , Cheng Yang , Xinghua Chen , Maoqing Tian , Liwen Qiao , Jiefei Zeng , Wenjing Zhen , Wei Liang , Lunzhi Liu , Huiming Wang , Xiangyou Li , Lu Zhang
Cisplatin is widely used in treating solid tumors, but its dose-limiting nephrotoxicity, which manifests as acute kidney injury (AKI), remains a major clinical challenge. The molecular pathways determining proximal tubular epithelial cell (PTEC) susceptibility during cisplatin-induced injury are not fully elucidated. Here, we identify ubiquitin protein ligase E3 component n-recognin 4 (UBR4) as a key regulator of the integrated stress response (ISR), which plays an important role in regulating reactive oxygen species (ROS) accumulation and mitophagy in the kidney. UBR4 expression was markedly upregulated in PTECs of mice with cisplatin-induced AKI. Tubule-specific Ubr4 deficiency exacerbated kidney dysfunction, tubular damage, and cell death. Mechanistically, UBR4 promoted ubiquitination and degradation of the kinase HRI, thereby constraining ISR overactivation and alleviating its inhibitory effect on mitophagy. Consistent with this mechanism, both genetic enhancement of UBR4 and pharmacological inhibition of the ISR with ISRIB significantly mitigated cisplatin-induced nephrotoxicity. Together, our findings uncover a previously unrecognized UBR4-HRI-ISR regulatory axis that serves as an intrinsic protective mechanism in the kidney and highlight UBR4 as a promising therapeutic target for preventing cisplatin-induced tubular injury.
{"title":"UBR4 attenuates cisplatin-induced acute kidney injury by regulating the HRI-ISR axis","authors":"Zeyu Tang , Chen Li , Cheng Yang , Xinghua Chen , Maoqing Tian , Liwen Qiao , Jiefei Zeng , Wenjing Zhen , Wei Liang , Lunzhi Liu , Huiming Wang , Xiangyou Li , Lu Zhang","doi":"10.1016/j.freeradbiomed.2026.01.025","DOIUrl":"10.1016/j.freeradbiomed.2026.01.025","url":null,"abstract":"<div><div>Cisplatin is widely used in treating solid tumors, but its dose-limiting nephrotoxicity, which manifests as acute kidney injury (AKI), remains a major clinical challenge. The molecular pathways determining proximal tubular epithelial cell (PTEC) susceptibility during cisplatin-induced injury are not fully elucidated. Here, we identify ubiquitin protein ligase E3 component n-recognin 4 (UBR4) as a key regulator of the integrated stress response (ISR), which plays an important role in regulating reactive oxygen species (ROS) accumulation and mitophagy in the kidney. UBR4 expression was markedly upregulated in PTECs of mice with cisplatin-induced AKI. Tubule-specific <em>Ubr4</em> deficiency exacerbated kidney dysfunction, tubular damage, and cell death. Mechanistically, UBR4 promoted ubiquitination and degradation of the kinase HRI, thereby constraining ISR overactivation and alleviating its inhibitory effect on mitophagy. Consistent with this mechanism, both genetic enhancement of UBR4 and pharmacological inhibition of the ISR with ISRIB significantly mitigated cisplatin-induced nephrotoxicity. Together, our findings uncover a previously unrecognized UBR4-HRI-ISR regulatory axis that serves as an intrinsic protective mechanism in the kidney and highlight UBR4 as a promising therapeutic target for preventing cisplatin-induced tubular injury.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 269-289"},"PeriodicalIF":8.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.freeradbiomed.2026.01.013
Yanjun Zheng , Li Chen , Hongqi Li , Jingrong Lin , Jian Ma
Sepsis is a heterogeneous syndrome triggered by a dysregulated host response to infection, with glycolysis playing a vital role in maintaining macrophage immune function, which is critical for immune homeostasis and host survival during severe sepsis. Targeting glycolytic enzymes may offer effective strategies to mitigate macrophage-mediated inflammatory responses during sepsis. This study investigated the anti-inflammatory and metabolic modulatory effects of Orientin (Ori) in murine models of endotoxemia and sepsis, with a particular focus on its interaction with the glycolytic enzyme phosphofructokinase liver type (PFKL). Ori was administered at varying dosages in vivo, while in vitro experiments involved lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and RAW264.7 cells. Inflammatory responses were assessed using Western blot, Enzyme-Linked Immunosorbent Assay (ELISA), and immunofluorescence, while glycolytic activity was evaluated through lactate production, glucose uptake, and extracellular acidification rate (ECAR). Cellular Thermal Shift Assay (CETSA) and molecular docking confirmed the direct binding between Ori and PFKL, and further analyses using network pharmacology and PFKL overexpression elucidated the enzyme's role in mediating Ori's effects. Ori significantly improved survival, reduced lung injury, and suppressed cytokine release in septic mice, while in vitro it attenuated LPS-induced inflammatory cytokine expression and glycolysis. Notably, macrophage-specific PFKL overexpression abrogated Ori's protective effects. These findings demonstrate that Ori alleviates sepsis-induced inflammation and metabolic dysfunction by directly targeting PFKL, highlighting its potential as a novel therapeutic candidate for sepsis.
{"title":"Orientin alleviates severe inflammation via regulating macrophage glycolysis and immune function in sepsis","authors":"Yanjun Zheng , Li Chen , Hongqi Li , Jingrong Lin , Jian Ma","doi":"10.1016/j.freeradbiomed.2026.01.013","DOIUrl":"10.1016/j.freeradbiomed.2026.01.013","url":null,"abstract":"<div><div>Sepsis is a heterogeneous syndrome triggered by a dysregulated host response to infection, with glycolysis playing a vital role in maintaining macrophage immune function, which is critical for immune homeostasis and host survival during severe sepsis. Targeting glycolytic enzymes may offer effective strategies to mitigate macrophage-mediated inflammatory responses during sepsis. This study investigated the anti-inflammatory and metabolic modulatory effects of Orientin (Ori) in murine models of endotoxemia and sepsis, with a particular focus on its interaction with the glycolytic enzyme phosphofructokinase liver type (PFKL). Ori was administered at varying dosages in vivo, while in vitro experiments involved lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and RAW264.7 cells. Inflammatory responses were assessed using Western blot, Enzyme-Linked Immunosorbent Assay (ELISA), and immunofluorescence, while glycolytic activity was evaluated through lactate production, glucose uptake, and extracellular acidification rate (ECAR). Cellular Thermal Shift Assay (CETSA) and molecular docking confirmed the direct binding between Ori and PFKL, and further analyses using network pharmacology and PFKL overexpression elucidated the enzyme's role in mediating Ori's effects. Ori significantly improved survival, reduced lung injury, and suppressed cytokine release in septic mice, while in vitro it attenuated LPS-induced inflammatory cytokine expression and glycolysis. Notably, macrophage-specific PFKL overexpression abrogated Ori's protective effects. These findings demonstrate that Ori alleviates sepsis-induced inflammation and metabolic dysfunction by directly targeting PFKL, highlighting its potential as a novel therapeutic candidate for sepsis.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 196-208"},"PeriodicalIF":8.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.freeradbiomed.2025.12.049
Susan Robinson , Reginald Davies , Viktoria Vagany , Timothy W. Gant , Andrew G. Smith
Metabolic disorders can be the consequence of external factors and individual susceptibility. Sporadic porphyria cutanea tarda (sPCT) is an idiopathic disorder of liver heme synthesis exhibiting inhibition of uroporphyrinogen decarboxylase, characterised by dermal and hepatic deposition of uroporphyrins from oxidation of sensitive uroporphyrinogens (uroporphyria). sPCT is associated with alcohol, estrogenic drugs, HIV and hepatitis C, as well as a poorly understood influence of iron. Hexachlorobenzene (HCB) and reputably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a similar disorder. The hepatic aspects modelled in susceptible rodents in response to HCB and TCDD are potentiated by iron. Importantly, iron overload alone eventually causes hepatic uroporphyria in genetically susceptible mice. To determine whether this genetic susceptibility to iron toxicity is the consequence of a single genetic variant or is multigenic, a low power F2 intercross cross from sensitive SWR and resistant DBA/2 strains was used to detect chromosomal quantitative trait loci (QTL) associated with uroporphyria development enhanced by the heme precursor 5-aminolevulinic acid (5-ALA). Multiple QTL contributed to the development of uroporphyria. Differential gene expressions comparing mice of parent strains and the F2 extremes of resistance and susceptibility suggested possible contributions associated with QTL. Positions of QTL and the confidence regions were compared with those observed previously for uroporphyria induced more rapidly by TCDD in iron-loaded mice and showed overlapping but not identical loci. A difference in uroporphyric response to iron loading occurred with another sensitive strain, C57BL/10ScSn, whether maintained on one of two well-defined, but similar, same source commercial diets. Uroporphyria developed with a nutritionally enhanced diet rather than a lean maintenance diet. One common observation with uroporphyria was decreased expression of Glul for glutamine synthetase. The findings illustrate the interaction of polygenic factors, external factors and diet in models of idiopathic human disorders such as sPCT.
{"title":"Genetic traits and diet triggering the iron-induced hepatic model of the idiopathic disorder sporadic porphyria cutanea tarda","authors":"Susan Robinson , Reginald Davies , Viktoria Vagany , Timothy W. Gant , Andrew G. Smith","doi":"10.1016/j.freeradbiomed.2025.12.049","DOIUrl":"10.1016/j.freeradbiomed.2025.12.049","url":null,"abstract":"<div><div>Metabolic disorders can be the consequence of external factors and individual susceptibility. Sporadic porphyria cutanea tarda (sPCT) is an idiopathic disorder of liver heme synthesis exhibiting inhibition of uroporphyrinogen decarboxylase, characterised by dermal and hepatic deposition of uroporphyrins from oxidation of sensitive uroporphyrinogens (uroporphyria). sPCT is associated with alcohol, estrogenic drugs, HIV and hepatitis C, as well as a poorly understood influence of iron. Hexachlorobenzene (HCB) and reputably 2,3,7,8-tetrachlorodibenzo-<em>p</em>-dioxin (TCDD) cause a similar disorder. The hepatic aspects modelled in susceptible rodents in response to HCB and TCDD are potentiated by iron. Importantly, iron overload alone eventually causes hepatic uroporphyria in genetically susceptible mice. To determine whether this genetic susceptibility to iron toxicity is the consequence of a single genetic variant or is multigenic, a low power F2 intercross cross from sensitive SWR and resistant DBA/2 strains was used to detect chromosomal quantitative trait loci (QTL) associated with uroporphyria development enhanced by the heme precursor 5-aminolevulinic acid (5-ALA). Multiple QTL contributed to the development of uroporphyria. Differential gene expressions comparing mice of parent strains and the F2 extremes of resistance and susceptibility suggested possible contributions associated with QTL. Positions of QTL and the confidence regions were compared with those observed previously for uroporphyria induced more rapidly by TCDD in iron-loaded mice and showed overlapping but not identical loci. A difference in uroporphyric response to iron loading occurred with another sensitive strain, C57BL/10ScSn, whether maintained on one of two well-defined, but similar, same source commercial diets. Uroporphyria developed with a nutritionally enhanced diet rather than a lean maintenance diet. One common observation with uroporphyria was decreased expression of <em>Glul</em> for glutamine synthetase. The findings illustrate the interaction of polygenic factors, external factors and diet in models of idiopathic human disorders such as sPCT.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 126-139"},"PeriodicalIF":8.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.freeradbiomed.2026.01.017
Xinli Hu , Haojie Zhang , Zheng Wang , Xuan Zhao , Tao Hu , Chengxin Liu , Xiaolong Chen , Wei Wang , Shibao Lu
Osteoporosis is driven in large part by excessive osteoclast-mediated bone resorption, and exercise-induced myokines such as irisin have emerged as potential modulators of bone remodeling, yet the mechanism by which irisin regulates osteoclastogenesis remains incompletely defined. Here, we integrated clinical analyses, mechanistic cell studies, and ovariectomized (OVX) mouse models to determine whether irisin protects against estrogen deficiency–induced bone loss and to delineate the underlying signaling axis. In 109 postmenopausal women, circulating irisin levels were positively associated with bone mineral density and inversely correlated with the bone resorption marker β-CTX. In vitro, irisin dose-dependently suppressed RANKL-induced osteoclast differentiation, F-actin ring formation, and resorption activity in bone marrow–derived macrophages, accompanied by downregulation of osteoclast marker genes and proteins. Mechanistically, network pharmacology and molecular docking, together with CETSA, co-immunoprecipitation, and immunofluorescence, supported a direct irisin–Nrf2 interaction; irisin stabilized Nrf2 and thereby restrained TRAF6-mediated K63-linked ubiquitination and activation of STING, resulting in attenuation of downstream NF-κB signaling. In vivo, irisin administration improved trabecular microarchitecture and reduced osteoclast number/activity in OVX mice, whereas these protective effects were largely abolished in Nrf2-deficient mice, indicating an Nrf2-dependent mechanism. Collectively, our findings identify an Irisin–Nrf2–STING/NF-κB axis that suppresses osteoclastogenesis and mitigates estrogen deficiency–induced bone loss, supporting irisin as a promising therapeutic candidate for osteoporosis.
{"title":"Exercise-derived irisin prevents bone loss via Nrf2 activation and inhibition of STING/NF-κB signaling","authors":"Xinli Hu , Haojie Zhang , Zheng Wang , Xuan Zhao , Tao Hu , Chengxin Liu , Xiaolong Chen , Wei Wang , Shibao Lu","doi":"10.1016/j.freeradbiomed.2026.01.017","DOIUrl":"10.1016/j.freeradbiomed.2026.01.017","url":null,"abstract":"<div><div>Osteoporosis is driven in large part by excessive osteoclast-mediated bone resorption, and exercise-induced myokines such as irisin have emerged as potential modulators of bone remodeling, yet the mechanism by which irisin regulates osteoclastogenesis remains incompletely defined. Here, we integrated clinical analyses, mechanistic cell studies, and ovariectomized (OVX) mouse models to determine whether irisin protects against estrogen deficiency–induced bone loss and to delineate the underlying signaling axis. In 109 postmenopausal women, circulating irisin levels were positively associated with bone mineral density and inversely correlated with the bone resorption marker β-CTX. In vitro, irisin dose-dependently suppressed RANKL-induced osteoclast differentiation, F-actin ring formation, and resorption activity in bone marrow–derived macrophages, accompanied by downregulation of osteoclast marker genes and proteins. Mechanistically, network pharmacology and molecular docking, together with CETSA, co-immunoprecipitation, and immunofluorescence, supported a direct irisin–Nrf2 interaction; irisin stabilized Nrf2 and thereby restrained TRAF6-mediated K63-linked ubiquitination and activation of STING, resulting in attenuation of downstream NF-κB signaling. In vivo, irisin administration improved trabecular microarchitecture and reduced osteoclast number/activity in OVX mice, whereas these protective effects were largely abolished in Nrf2-deficient mice, indicating an Nrf2-dependent mechanism. Collectively, our findings identify an Irisin–Nrf2–STING/NF-κB axis that suppresses osteoclastogenesis and mitigates estrogen deficiency–induced bone loss, supporting irisin as a promising therapeutic candidate for osteoporosis.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 51-68"},"PeriodicalIF":8.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.freeradbiomed.2026.01.012
Weiwei Wang , Zhenghui Wang , Fujie Wang , Ying Li , Haoyang Zhou , Yanan Pu , Xufeng Chen , Yi Jiang
Background
Sepsis-induced cardiomyopathy (SICM) is one of the leading causes of mortality in sepsis patients, and currently, there are no effective treatments available. Ferroptosis has been proven to play a critical role in SICM. Exosomes from the young healthy human plasma (exosomesYoung) were shown to improve cardiac fibrosis post-myocardial infarction in our previous studies. However, their role in SICM remains unclear.
Methods
We established in vivo and in vitro models of SICM induced by lipopolysaccharide (LPS). The severity of cardiac and cardiomyocyte injury was evaluated through echocardiography, histological analysis, measurements of myocardial injury markers, and cell viability assays. Improvements in SICM via inhibition of ferroptosis by exosomesYoung were demonstrated by assessing ferroptosis-related indicators, including Fe2+, malondialdehyde (MDA), Liperfluo (LPO) levels, PTGS2 expression, and mitochondrial structural integrity.
Results
In this study, we demonstrated that exosomesYoung significantly improved cardiac function and mitigated morphological damage in the hearts of mice with SICM. ExosomesYoung also enhanced the viability of LPS-induced cardiomyocytes, reduced levels of lipid peroxides and ferroptosis biomarkers, and suppressed ROS production, mitochondrial membrane potential reduction, and mitochondrial ultrastructural damage. Mechanistically, high-throughput sequencing analysis followed by qRT-PCR validation identified miR-3130-3p as a key effector molecule. Upregulation of miR-3130-3p mimicked the therapeutic effects of exosomesYoung on LPS-induced cardiac injury and mediated the cardioprotective role of exosomesYoung against ferroptosis in SICM. Further, target gene prediction using databases and validation with a dual-luciferase reporter assay confirmed LPCAT3 as the direct target gene of miR-3130-3p in inhibiting ferroptosis. Overexpression of LPCAT3 could reverse the protective effects of miR-3130-3p on LPS-induced SICM.
Conclusions
In summary, these findings reveal for the first time that exosomesYoung improve SICM by inhibiting ferroptosis via miR-3130-3p targeting LPCAT3. This study provides novel insights into the potential of exosomesYoung as promising cardioprotective candidates for patients with SICM.
{"title":"Exosomes from young healthy human plasma ameliorate sepsis-induced cardiomyopathy by inhibiting ferroptosis via the miR-3130-3p/LPCAT3 axis","authors":"Weiwei Wang , Zhenghui Wang , Fujie Wang , Ying Li , Haoyang Zhou , Yanan Pu , Xufeng Chen , Yi Jiang","doi":"10.1016/j.freeradbiomed.2026.01.012","DOIUrl":"10.1016/j.freeradbiomed.2026.01.012","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced cardiomyopathy (SICM) is one of the leading causes of mortality in sepsis patients, and currently, there are no effective treatments available. Ferroptosis has been proven to play a critical role in SICM. Exosomes from the young healthy human plasma (exosomes<sup>Young</sup>) were shown to improve cardiac fibrosis post-myocardial infarction in our previous studies. However, their role in SICM remains unclear.</div></div><div><h3>Methods</h3><div>We established <em>in vivo</em> and <em>in vitro</em> models of SICM induced by lipopolysaccharide (LPS). The severity of cardiac and cardiomyocyte injury was evaluated through echocardiography, histological analysis, measurements of myocardial injury markers, and cell viability assays. Improvements in SICM <em>via</em> inhibition of ferroptosis by exosomes<sup>Young</sup> were demonstrated by assessing ferroptosis-related indicators, including Fe<sup>2+</sup>, malondialdehyde (MDA), Liperfluo (LPO) levels, PTGS2 expression, and mitochondrial structural integrity.</div></div><div><h3>Results</h3><div>In this study, we demonstrated that exosomes<sup>Young</sup> significantly improved cardiac function and mitigated morphological damage in the hearts of mice with SICM. Exosomes<sup>Young</sup> also enhanced the viability of LPS-induced cardiomyocytes, reduced levels of lipid peroxides and ferroptosis biomarkers, and suppressed ROS production, mitochondrial membrane potential reduction, and mitochondrial ultrastructural damage. Mechanistically, high-throughput sequencing analysis followed by qRT-PCR validation identified miR-3130-3p as a key effector molecule. Upregulation of miR-3130-3p mimicked the therapeutic effects of exosomes<sup>Young</sup> on LPS-induced cardiac injury and mediated the cardioprotective role of exosomes<sup>Young</sup> against ferroptosis in SICM. Further, target gene prediction using databases and validation with a dual-luciferase reporter assay confirmed LPCAT3 as the direct target gene of miR-3130-3p in inhibiting ferroptosis. Overexpression of LPCAT3 could reverse the protective effects of miR-3130-3p on LPS-induced SICM.</div></div><div><h3>Conclusions</h3><div>In summary, these findings reveal for the first time that exosomes<sup>Young</sup> improve SICM by inhibiting ferroptosis <em>via</em> miR-3130-3p targeting LPCAT3. This study provides novel insights into the potential of exosomes<sup>Young</sup> as promising cardioprotective candidates for patients with SICM.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 140-158"},"PeriodicalIF":8.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.freeradbiomed.2026.01.023
A J García-Yagüe, N Esteras, A T Dinkova-Kostova, A I Rojo, P G Shiels, A Dinnyes, V Tamas, H van Goor, I Lastres-Becker
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuronal loss, α-SYNUCLEIN aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) orchestrates cellular defense mechanisms by controlling genes involved in antioxidant responses, detoxification, and proteostasis. Impaired NRF2 signaling in PD amplifies oxidative damage, protein misfolding, and inflammatory cascades, whereas NRF2 activation confers broad neuroprotection. This review summarizes evidence from cellular, animal, and human studies delineating NRF2 regulatory roles in redox homeostasis, mitochondrial integrity, and microglial activation. In preclinical models, NRF2 deficiency accelerates neurodegeneration, while pharmacological activation with agents such as dimethyl fumarate, sulforaphane, and synthetic triterpenoids mitigates dopaminergic loss and neuroinflammation. Human studies reveal altered NRF2 pathway components in PD brain and peripheral tissues, and genetic variants in NFE2L2 influence disease susceptibility and progression. Aging, PD's strongest risk factor, reduces NRF2 responsiveness through epigenetic and post-translational changes, promoting oxidative vulnerability and inflammaging. Environmental exposures, including pesticides and pollutants, further modulate NRF2 activity, compounding risk via cumulative "exposome" effects. Understanding NRF2 regulation provides mechanistic insight into PD pathogenesis and positions NRF2 activation as a promising therapeutic strategy for disease modification and healthy brain aging.
{"title":"NRF2 at the crossroads of Parkinson's disease and aging: Mechanistic insights and translational perspectives.","authors":"A J García-Yagüe, N Esteras, A T Dinkova-Kostova, A I Rojo, P G Shiels, A Dinnyes, V Tamas, H van Goor, I Lastres-Becker","doi":"10.1016/j.freeradbiomed.2026.01.023","DOIUrl":"10.1016/j.freeradbiomed.2026.01.023","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuronal loss, α-SYNUCLEIN aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) orchestrates cellular defense mechanisms by controlling genes involved in antioxidant responses, detoxification, and proteostasis. Impaired NRF2 signaling in PD amplifies oxidative damage, protein misfolding, and inflammatory cascades, whereas NRF2 activation confers broad neuroprotection. This review summarizes evidence from cellular, animal, and human studies delineating NRF2 regulatory roles in redox homeostasis, mitochondrial integrity, and microglial activation. In preclinical models, NRF2 deficiency accelerates neurodegeneration, while pharmacological activation with agents such as dimethyl fumarate, sulforaphane, and synthetic triterpenoids mitigates dopaminergic loss and neuroinflammation. Human studies reveal altered NRF2 pathway components in PD brain and peripheral tissues, and genetic variants in NFE2L2 influence disease susceptibility and progression. Aging, PD's strongest risk factor, reduces NRF2 responsiveness through epigenetic and post-translational changes, promoting oxidative vulnerability and inflammaging. Environmental exposures, including pesticides and pollutants, further modulate NRF2 activity, compounding risk via cumulative \"exposome\" effects. Understanding NRF2 regulation provides mechanistic insight into PD pathogenesis and positions NRF2 activation as a promising therapeutic strategy for disease modification and healthy brain aging.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"760-779"},"PeriodicalIF":8.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA), a common degenerative joint disorder, currently lacks effective therapeutic strategies to alleviate its progression. This study aims to investigate the function and underlying mechanisms of dihydrolipoic acid (DHLA) in inhibiting ferroptosis in chondrocytes and alleviating OA progression.
Methods
Mouse primary chondrocytes were exposed to IL-1β to induce ferroptosis and treated with DHLA in vitro, followed by the assessment of ferroptosis-related markers and indicators of chondrocyte anabolism and catabolism. The underlying therapeutic mechanisms of DHLA in OA were further investigated through computer network analysis and experimental validation. The surgery destabilization of the medial meniscus was then conducted to establish the mouse OA model before treatment with DHLA. The therapeutic effect of DHLA in OA mice was evaluated through micro-CT and histological analyses.
Results
DHLA suppressed the IL-1β-induced increases in levels of intracellular reactive oxygen species, Fe2+, lipid peroxidation, and malondialdehyde in chondrocytes, while attenuating the depletion of glutathione, as well as the levels of GPX4 and SLC7A11. Furthermore, the IL-1β-induced reductions in proteoglycans secretion and the levels of Collagen II, Aggrecan, and SOX9 were attenuated by DHLA, while inhibiting the upregulation of MMP13, MMP3, and ADAMTS5. Further studies revealed that the downregulation of FOXO1 expression and the upregulation of TXNIP expression induced by IL-1β were ameliorated by DHLA. The protective effects of DHLA were abolished by AS1842856, a specific FOXO1 inhibitor, whereas this inhibition was reversed by SRI-37330, a specific TXNIP inhibitor. In vivo, DHLA attenuated osteophyte formation and cartilage degeneration induced by DMM surgery in OA model mice. Moreover, the upregulation of MMP13 and TXNIP was suppressed by DHLA, as well as the downregulation of Collagen II, GPX4, and FOXO1 in articular cartilage.
Conclusion
DHLA inhibits chondrocytes ferroptosis to alleviate OA progression through the FOXO1/TXNIP signaling pathway, offering a potential treatment strategy for OA.
{"title":"Dihydrolipoic acid suppresses ferroptosis in chondrocytes to ameliorate the progression of osteoarthritis by modulating the FOXO1/TXNIP signaling pathway","authors":"Yitao Chen , Jiawei Fang , Zhiguo Zhou , Haiwei Ma, Shijie Liu, Hehuan Lai, Yahong Lu, Yu Bai, XingYu Hu, Zhenzhong Chen, Feijun Liu, Dengwei He","doi":"10.1016/j.freeradbiomed.2026.01.021","DOIUrl":"10.1016/j.freeradbiomed.2026.01.021","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA), a common degenerative joint disorder, currently lacks effective therapeutic strategies to alleviate its progression. This study aims to investigate the function and underlying mechanisms of dihydrolipoic acid (DHLA) in inhibiting ferroptosis in chondrocytes and alleviating OA progression.</div></div><div><h3>Methods</h3><div>Mouse primary chondrocytes were exposed to IL-1β to induce ferroptosis and treated with DHLA in vitro, followed by the assessment of ferroptosis-related markers and indicators of chondrocyte anabolism and catabolism. The underlying therapeutic mechanisms of DHLA in OA were further investigated through computer network analysis and experimental validation. The surgery destabilization of the medial meniscus was then conducted to establish the mouse OA model before treatment with DHLA. The therapeutic effect of DHLA in OA mice was evaluated through micro-CT and histological analyses.</div></div><div><h3>Results</h3><div>DHLA suppressed the IL-1β-induced increases in levels of intracellular reactive oxygen species, Fe<sup>2+</sup>, lipid peroxidation, and malondialdehyde in chondrocytes, while attenuating the depletion of glutathione, as well as the levels of GPX4 and SLC7A11. Furthermore, the IL-1β-induced reductions in proteoglycans secretion and the levels of Collagen II, Aggrecan, and SOX9 were attenuated by DHLA, while inhibiting the upregulation of MMP13, MMP3, and ADAMTS5. Further studies revealed that the downregulation of FOXO1 expression and the upregulation of TXNIP expression induced by IL-1β were ameliorated by DHLA. The protective effects of DHLA were abolished by AS1842856, a specific FOXO1 inhibitor, whereas this inhibition was reversed by SRI-37330, a specific TXNIP inhibitor. In vivo, DHLA attenuated osteophyte formation and cartilage degeneration induced by DMM surgery in OA model mice. Moreover, the upregulation of MMP13 and TXNIP was suppressed by DHLA, as well as the downregulation of Collagen II, GPX4, and FOXO1 in articular cartilage.</div></div><div><h3>Conclusion</h3><div>DHLA inhibits chondrocytes ferroptosis to alleviate OA progression through the FOXO1/TXNIP signaling pathway, offering a potential treatment strategy for OA.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 169-180"},"PeriodicalIF":8.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.freeradbiomed.2026.01.016
Zhuolin Du , Xingwu Liu , Yanhan Yang , Xudong Min , Jirui Wei , Yang She , Abudushalamu Abulaiti , Xiayu Jin , Zequn Su , Shizhong Zhang , Jian Liu , Karrie M. Kiang , Gilberto Ka-Kit Leung , Xiaozheng He , Zhiyuan Zhu
Mitochondrial integrity is essential for tumor cell proliferation and survival. Our previous study has demonstrated the oncogenic role of the metabolic enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in glioblastoma (GBM). Given that the non-metabolic function of certain enzymes has been reported, we aim to interrogate whether MTHFD2 has potential roles in mitochondrial integrity and dynamics, especially beyond catabolism. By using multi-faceted approaches including single-cell RNA sequencing, mt-Keima mitophagy flux assays, RNA immunoprecipitation sequencing and luciferase reporter assays, we elucidated a novel, non-canonical function of MTHFD2 in stabilizing mRNA in GBM. We found that MTHFD2 was upregulated in GBM and was enriched in specific tumor subtypes cells such as ependymal-like and OPC-like cells. Knockdown of MTHFD2 profoundly promoted mitochondrial fission that triggered excessive mitophagy and cellular apoptosis. Mechanistically, MTHFD2 directly bound to the 3′-untranslated region (3′-UTR) of TOP2A mRNA and enhanced its stability, implying the RNA binding function of this catabolic enzyme. Overexpression of TOP2A attenuated mitophagy and cellular apoptosis induced by MTHFD2 depletion, indicating a vital role of MTHFD2-TOP2A axis in modulating mitochondrial integrity. Importantly, targeting MTHFD2 impeded GBM growth in orthotopic mouse models, which could be a promising therapeutic strategy. In conclusion, we proposed a non-canonical function of MTHFD2, which bound to and stabilized the mRNA of TOP2A. Targeting MTHFD2 triggered excessive mitophagy and cell apoptosis in GBM via destabilizing TOP2A mRNA.
{"title":"The non-metabolic role of MTHFD2 in regulating mitochondrial fission-dependent mitophagy via stabilizing TOP2A mRNA in glioblastoma","authors":"Zhuolin Du , Xingwu Liu , Yanhan Yang , Xudong Min , Jirui Wei , Yang She , Abudushalamu Abulaiti , Xiayu Jin , Zequn Su , Shizhong Zhang , Jian Liu , Karrie M. Kiang , Gilberto Ka-Kit Leung , Xiaozheng He , Zhiyuan Zhu","doi":"10.1016/j.freeradbiomed.2026.01.016","DOIUrl":"10.1016/j.freeradbiomed.2026.01.016","url":null,"abstract":"<div><div>Mitochondrial integrity is essential for tumor cell proliferation and survival. Our previous study has demonstrated the oncogenic role of the metabolic enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in glioblastoma (GBM). Given that the non-metabolic function of certain enzymes has been reported, we aim to interrogate whether MTHFD2 has potential roles in mitochondrial integrity and dynamics, especially beyond catabolism. By using multi-faceted approaches including single-cell RNA sequencing, mt-Keima mitophagy flux assays, RNA immunoprecipitation sequencing and luciferase reporter assays, we elucidated a novel, non-canonical function of MTHFD2 in stabilizing mRNA in GBM. We found that MTHFD2 was upregulated in GBM and was enriched in specific tumor subtypes cells such as ependymal-like and OPC-like cells. Knockdown of MTHFD2 profoundly promoted mitochondrial fission that triggered excessive mitophagy and cellular apoptosis. Mechanistically, MTHFD2 directly bound to the 3′-untranslated region (3′-UTR) of TOP2A mRNA and enhanced its stability, implying the RNA binding function of this catabolic enzyme. Overexpression of TOP2A attenuated mitophagy and cellular apoptosis induced by MTHFD2 depletion, indicating a vital role of MTHFD2-TOP2A axis in modulating mitochondrial integrity. Importantly, targeting MTHFD2 impeded GBM growth in orthotopic mouse models, which could be a promising therapeutic strategy. In conclusion, we proposed a non-canonical function of MTHFD2, which bound to and stabilized the mRNA of TOP2A. Targeting MTHFD2 triggered excessive mitophagy and cell apoptosis in GBM via destabilizing TOP2A mRNA.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"246 ","pages":"Pages 93-106"},"PeriodicalIF":8.2,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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