Pub Date : 2026-01-01DOI: 10.1016/j.molimm.2025.11.018
Zuning Jiang , Ruojia Zhang , Ya Han , Ruiyao Sun , Mingze Kong , Yuang Zhang , Junling Li , Guanhua Song , Li Qiao , Lin Wang
Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme catalyzing spermidine synthesis-to RA pathogenesis remains undefined. It’s observed in this study that SMOX was responsible for inflammatory stimuli that its expression increased obviously when RA-associated fibroblast-like synoviocytes (FLSs) were challenged by inflammatory factors. Functionally, silencing SMOX could inhibit migration, invasion, and cytokine production, but induced apoptosis of RA-FLS. Moreover, inhibition of SMOX using JNJ-9350 yielded anti-inflammatory effects comparable to those achieved by gene silencing in RA-FLS. In vivo experiments demonstrated that JNJ-9350 could effectively reduce the severity of arthritis, minimize histopathological damage, and prevent bone erosion in collagen antibody-induced arthritis (CAIA) mice. The present results indicate that SMOX is implicated in the development of RA and suggest that targeting SMOX could be a novel treatment strategy.
{"title":"Investigating the role of SMOX in rheumatoid arthritis","authors":"Zuning Jiang , Ruojia Zhang , Ya Han , Ruiyao Sun , Mingze Kong , Yuang Zhang , Junling Li , Guanhua Song , Li Qiao , Lin Wang","doi":"10.1016/j.molimm.2025.11.018","DOIUrl":"10.1016/j.molimm.2025.11.018","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme catalyzing spermidine synthesis-to RA pathogenesis remains undefined. It’s observed in this study that SMOX was responsible for inflammatory stimuli that its expression increased obviously when RA-associated fibroblast-like synoviocytes (FLSs) were challenged by inflammatory factors. Functionally, silencing SMOX could inhibit migration, invasion, and cytokine production, but induced apoptosis of RA-FLS. Moreover, inhibition of SMOX using JNJ-9350 yielded anti-inflammatory effects comparable to those achieved by gene silencing in RA-FLS. In vivo experiments demonstrated that JNJ-9350 could effectively reduce the severity of arthritis, minimize histopathological damage, and prevent bone erosion in collagen antibody-induced arthritis (CAIA) mice. The present results indicate that SMOX is implicated in the development of RA and suggest that targeting SMOX could be a novel treatment strategy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 235-246"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.molimm.2025.12.005
Jianlin He, Jue Li, Min Bai, Jie Yang
Objective
This study aimed to elucidate the molecular mechanisms through which CXCL2 contributes to the pathogenesis of idiopathic interstitial pneumonia (IIP).
Methods
Neutrophils were isolated, and the formation of neutrophil extracellular traps (NETs) was assessed after CXCL2 treatment. Cellular concentrations of cell-free DNA (cf-DNA) were quantified via a cf-DNA/NET kit. Additionally, an enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of IL-6, TNF-α, and LL-37. Western blot analysis was used to measure the levels of LC3-II, LC3-I, citrullinated histone H3 (citH3), myeloperoxidase (MPO), and elastase. Immunohistochemistry was conducted to measure cit H3 levels. Pathological alterations in the lung tissue were examined via microscopic hemosiderin and eosin staining.
Results
CXCL2 treatment significantly increased the cellular expression levels of cf-DNA, IL-6, TNF-α, and LL-37, as well as cit H3 and MPO, which are markers of NETs. Furthermore, CXCL2 treatment induced a substantial increase in cellular autophagy. Additionally, CXCL2 treatment led to marked upregulation of TLR4 expression and further elevation of autophagy levels, accompanied by increases in cf-DNA, IL-6, TNF-α, and LL-37 expression. Inhibition of TLR4 expression significantly reduced the levels of these factors. Moreover, the CXCL2-induced upregulation of cf-DNA, IL-6, TNF-α, LL-37, cit H3, and MPO was notably suppressed following the knockdown of ATG7. In IIP murine models, there was a significant upregulation of cf-DNA, IL-6, TNF-α, and LL-37, as well as an increase in cit H3 and MPO expression. Lung tissue analysis revealed inflammatory cell infiltration, alveolar wall thickening, tissue congestion, and edema. Inhibition of CXCL2 and TLR4 expression significantly ameliorated these pathological changes.
Conclusions
The CXCL2TLR4 axis may facilitate NET activation by promoting autophagy via ATG7, thereby contributing to IIP progression.
{"title":"CXCL2-TLR4 axis activates NETs by accelerating autophagy through ATG7 to promote the progression of idiopathic interstitial pneumonia","authors":"Jianlin He, Jue Li, Min Bai, Jie Yang","doi":"10.1016/j.molimm.2025.12.005","DOIUrl":"10.1016/j.molimm.2025.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to elucidate the molecular mechanisms through which CXCL2 contributes to the pathogenesis of idiopathic interstitial pneumonia (IIP).</div></div><div><h3>Methods</h3><div>Neutrophils were isolated, and the formation of neutrophil extracellular traps (NETs) was assessed after CXCL2 treatment. Cellular concentrations of cell-free DNA (cf-DNA) were quantified via a cf-DNA/NET kit. Additionally, an enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of IL-6, TNF-α, and LL-37. Western blot analysis was used to measure the levels of LC3-II, LC3-I, citrullinated histone H3 (citH3), myeloperoxidase (MPO), and elastase. Immunohistochemistry was conducted to measure cit H3 levels. Pathological alterations in the lung tissue were examined via microscopic hemosiderin and eosin staining.</div></div><div><h3>Results</h3><div>CXCL2 treatment significantly increased the cellular expression levels of cf-DNA, IL-6, TNF-α, and LL-37, as well as cit H3 and MPO, which are markers of NETs. Furthermore, CXCL2 treatment induced a substantial increase in cellular autophagy. Additionally, CXCL2 treatment led to marked upregulation of TLR4 expression and further elevation of autophagy levels, accompanied by increases in cf-DNA, IL-6, TNF-α, and LL-37 expression. Inhibition of TLR4 expression significantly reduced the levels of these factors. Moreover, the CXCL2-induced upregulation of cf-DNA, IL-6, TNF-α, LL-37, cit H3, and MPO was notably suppressed following the knockdown of ATG7. In IIP murine models, there was a significant upregulation of cf-DNA, IL-6, TNF-α, and LL-37, as well as an increase in cit H3 and MPO expression. Lung tissue analysis revealed inflammatory cell infiltration, alveolar wall thickening, tissue congestion, and edema. Inhibition of CXCL2 and TLR4 expression significantly ameliorated these pathological changes.</div></div><div><h3>Conclusions</h3><div>The CXCL2<img>TLR4 axis may facilitate NET activation by promoting autophagy via ATG7, thereby contributing to IIP progression.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 226-234"},"PeriodicalIF":3.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.molimm.2025.11.013
Si Li , Chengwu Liu , Caixia Wu , Zhaoming Liu
Background
Sepsis, a life-threatening condition, involves excessive neutrophil extracellular traps (NETs) contributing to organ damage. The role of orphan nuclear receptor NR4A3 in modulating neutrophil NETosis via NF-κB during sepsis is poorly understood. This study aimed to elucidate NR4A3's function and therapeutic potential.
Methods
Single-cell RNA sequencing analysis was performed using GSE175453 and GSE167363 from GEO database, involving PBMCs from septic patients and controls. In vitro, ATRA-differentiated HL-60 neutrophils with NR4A3 overexpression were LPS-stimulated. In vivo, a cecal ligation and puncture (CLP) sepsis mouse model received AAV-mediated NR4A3 overexpression. Key readouts included NR4A3 expression, NF-κB activation, NETs markers (NE, CitH3, PADI4, MPO-DNA), inflammatory cytokines (TNF-α, IL-1β, IL-6), ROS generation, and intestinal tissue pathology.
Results
scRNA-seq analysis revealed significant NR4A3 downregulation in neutrophils from septic patients. In vitro, NR4A3 overexpression in neutrophils significantly attenuated LPS-induced NF-κB (p65) activation, NETs formation, inflammatory cytokine production, and ROS generation. In vivo, AAV-mediated NR4A3 overexpression in CLP-induced septic mice ameliorated intestinal inflammation, suppressed p65 phosphorylation and NETs-related markers in the intestine, and reduced systemic inflammatory cytokine levels.
Conclusion
Our findings demonstrate that NR4A3 exerts a protective role in sepsis by inhibiting the NF-κB signaling pathway in neutrophils, thereby suppressing excessive NETs formation and the associated inflammatory cascade. Thus, NR4A3 represents a promising therapeutic target for mitigating NET-driven pathology in sepsis.
{"title":"Restoring NR4A3 function in neutrophils alleviates sepsis by limiting NF-κB-dependent NETs formation and organ damage","authors":"Si Li , Chengwu Liu , Caixia Wu , Zhaoming Liu","doi":"10.1016/j.molimm.2025.11.013","DOIUrl":"10.1016/j.molimm.2025.11.013","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis, a life-threatening condition, involves excessive neutrophil extracellular traps (NETs) contributing to organ damage. The role of orphan nuclear receptor NR4A3 in modulating neutrophil NETosis via NF-κB during sepsis is poorly understood. This study aimed to elucidate NR4A3's function and therapeutic potential.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing analysis was performed using GSE175453 and GSE167363 from GEO database, involving PBMCs from septic patients and controls. <em>In vitro</em>, ATRA-differentiated HL-60 neutrophils with NR4A3 overexpression were LPS-stimulated. <em>In vivo</em>, a cecal ligation and puncture (CLP) sepsis mouse model received AAV-mediated NR4A3 overexpression. Key readouts included NR4A3 expression, NF-κB activation, NETs markers (NE, CitH3, PADI4, MPO-DNA), inflammatory cytokines (TNF-α, IL-1β, IL-6), ROS generation, and intestinal tissue pathology.</div></div><div><h3>Results</h3><div>scRNA-seq analysis revealed significant NR4A3 downregulation in neutrophils from septic patients. In vitro, NR4A3 overexpression in neutrophils significantly attenuated LPS-induced NF-κB (p65) activation, NETs formation, inflammatory cytokine production, and ROS generation. In vivo, AAV-mediated NR4A3 overexpression in CLP-induced septic mice ameliorated intestinal inflammation, suppressed p65 phosphorylation and NETs-related markers in the intestine, and reduced systemic inflammatory cytokine levels.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that NR4A3 exerts a protective role in sepsis by inhibiting the NF-κB signaling pathway in neutrophils, thereby suppressing excessive NETs formation and the associated inflammatory cascade. Thus, NR4A3 represents a promising therapeutic target for mitigating NET-driven pathology in sepsis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 206-215"},"PeriodicalIF":3.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.molimm.2025.11.020
Chuankui Li, Yifan Yang, Qicai Li, Guowen Wang, Tao Tao, Lixiang Li, Haiwei Sang
Background
Non-small cell lung cancer (NSCLC) is the malignancy with the highest mortality worldwide. Circular RNA polo-like kinase 1 (circPLK1) is a circular RNA that involved in cancer progression. However, the role of circPLK1 in NSCLC requires further investigation.
Methods
The expression of circPLK1 in NSCLC cells was measured by using qRT-PCR. Bioinformatics analysis was performed to identify miRNAs that bind to circPLK1 and the target mRNAs of these miRNAs. Cell viability, proliferation, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, and Transwell assays, respectively. Protein expression was evaluated by western blotting. Xenograft models were established to verify the regulatory role of circPLK1 in the miR-1294/SLC16A9 axis.
Results
circPLK1 was upregulaterd in NSCLC cells. Silencing circPLK1 markedly inhibited cell viability, proliferation, migration, and invasion, while accelerating apoptosis in NSCLC cells. circPLK1 acted as a sponge for miR-1294 and promoted SLC16A9 expression in NSCLC cells. Knockdown of circPLK1 suppressed tumor growth in NSCLC by regulating the miR-1294/SLC16A9 axis.
Conclusion
circPLK1 silence inhibited the proliferation, migration, and invasion of NSCLC cells by regulating the miR-1294/SLC16A9 axis.
{"title":"Silence of circPLK1 inhibits NSCLC progression by regulating the miR-1294/SLC16A9 axis","authors":"Chuankui Li, Yifan Yang, Qicai Li, Guowen Wang, Tao Tao, Lixiang Li, Haiwei Sang","doi":"10.1016/j.molimm.2025.11.020","DOIUrl":"10.1016/j.molimm.2025.11.020","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the malignancy with the highest mortality worldwide. Circular RNA polo-like kinase 1 (<em>circPLK1</em>) is a circular RNA that involved in cancer progression. However, the role of <em>circPLK1</em> in NSCLC requires further investigation.</div></div><div><h3>Methods</h3><div>The expression of <em>circPLK1</em> in NSCLC cells was measured by using qRT-PCR. Bioinformatics analysis was performed to identify miRNAs that bind to <em>circPLK1</em> and the target mRNAs of these miRNAs. Cell viability, proliferation, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, and Transwell assays, respectively. Protein expression was evaluated by western blotting. Xenograft models were established to verify the regulatory role of circPLK1 in the miR-1294/SLC16A9 axis.</div></div><div><h3>Results</h3><div><em>circPLK1</em> was upregulaterd in NSCLC cells. Silencing <em>circPLK1</em> markedly inhibited cell viability, proliferation, migration, and invasion, while accelerating apoptosis in NSCLC cells. <em>circPLK1</em> acted as a sponge for <em>miR-1294</em> and promoted <em>SLC16A9</em> expression in NSCLC cells. Knockdown of <em>circPLK1</em> suppressed tumor growth in NSCLC by regulating the <em>miR-1294</em>/<em>SLC16A9</em> axis.</div></div><div><h3>Conclusion</h3><div><em>circPLK1</em> silence inhibited the proliferation, migration, and invasion of NSCLC cells by regulating the <em>miR-1294</em>/<em>SLC16A9</em> axis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 216-225"},"PeriodicalIF":3.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.molimm.2025.12.011
Yue Si , Biying Zhang , Jingjing Wei , Mengyun Li , Yong Liu , Hongwei Ma
Radiation-induced delayed brain injury (RIBI) refers to structural and functional brain alterations that develop several months to years after exposure to ionizing radiation (IR). Microglia activation-mediated neuroinflammation, as well as oxidative stress, constitutes a key factor contributing to RIBI. Indole-3-propionic acid (IPA) is an indole metabolite specifically produced by the tryptophan metabolism of gut microbiota. It can cross the blood-brain barrier and modulate the central nervous system (CNS). In order to explore the protective mechanism of IPA on IR-induced cerebral function, we studied the effect of IPA on the activation of BV2 microglia in vitro. The experimental results show that IPA can suppress the oxidative stress and inflammation of microglia, which is represented as upregulating the expression of antioxidant genes (Hmox1, Ho-1, and Nqo1), and reducing the mRNA levels of pro-inflammatory factors (Tnf-α, Il-6, Inos, and Nox2). This protective effect may be related to the inhibition of Wnt1 expression and STAT3 phosphorylation (p-STAT3 Y705; p = 0.0008) in microglia. Additionally, it was found that IPA could alleviate the IR-induced neuroinflammation and synaptic damage of mice, as evidenced by reduced serum TNF-α and IL-6 levels and widened postsynaptic density (PSD) thickness (p = 0.0239). Collectively, this study provides novel insights into the potential application of IPA in the therapeutic intervention of radiation-induced brain injury.
辐射诱发的延迟性脑损伤（RIBI）是指暴露于电离辐射（IR）数月至数年后发生的大脑结构和功能改变。小胶质细胞激活介导的神经炎症以及氧化应激是导致RIBI的关键因素。吲哚-3-丙酸（IPA）是肠道菌群色氨酸代谢特异性产生的吲哚代谢物。它可以穿过血脑屏障，调节中枢神经系统。为了探讨IPA对ir诱导的脑功能的保护机制，我们在体外研究了IPA对BV2小胶质细胞激活的影响。实验结果表明，IPA可以抑制小胶质细胞的氧化应激和炎症反应，表现为上调抗氧化基因（Hmox1、Ho-1、Nqo1）的表达，降低促炎因子（Tnf-α、Il-6、Inos、Nox2）的mRNA水平。这种保护作用可能与抑制小胶质细胞中Wnt1表达和STAT3磷酸化（p-STAT3 Y705; p = 0.0008）有关。此外，我们发现IPA可以减轻ir诱导的小鼠神经炎症和突触损伤，表现为降低血清TNF-α和IL-6水平，扩大突触后密度（PSD）厚度（p = 0.0239）。总的来说，本研究为IPA在辐射性脑损伤治疗干预中的潜在应用提供了新的见解。
{"title":"Indole-3-propionic acid exerts radio-protective effects by modulating Wnt1/STAT3 pathway to alleviate oxidative stress and neuroinflammation in microglia","authors":"Yue Si , Biying Zhang , Jingjing Wei , Mengyun Li , Yong Liu , Hongwei Ma","doi":"10.1016/j.molimm.2025.12.011","DOIUrl":"10.1016/j.molimm.2025.12.011","url":null,"abstract":"<div><div>Radiation-induced delayed brain injury (RIBI) refers to structural and functional brain alterations that develop several months to years after exposure to ionizing radiation (IR). Microglia activation-mediated neuroinflammation, as well as oxidative stress, constitutes a key factor contributing to RIBI. Indole-3-propionic acid (IPA) is an indole metabolite specifically produced by the tryptophan metabolism of gut microbiota. It can cross the blood-brain barrier and modulate the central nervous system (CNS). In order to explore the protective mechanism of IPA on IR-induced cerebral function, we studied the effect of IPA on the activation of BV2 microglia <em>in vitro</em>. The experimental results show that IPA can suppress the oxidative stress and inflammation of microglia, which is represented as upregulating the expression of antioxidant genes (<em>Hmox1</em>, <em>Ho-1</em>, and <em>Nqo1</em>), and reducing the mRNA levels of pro-inflammatory factors (<em>Tnf-α</em>, <em>Il-6</em>, <em>Inos</em>, and <em>Nox2</em>). This protective effect may be related to the inhibition of Wnt1 expression and STAT3 phosphorylation (p-STAT3 Y705; <em>p</em> = 0.0008) in microglia. Additionally, it was found that IPA could alleviate the IR-induced neuroinflammation and synaptic damage of mice, as evidenced by reduced serum TNF-α and IL-6 levels and widened postsynaptic density (PSD) thickness (<em>p</em> = 0.0239). Collectively, this study provides novel insights into the potential application of IPA in the therapeutic intervention of radiation-induced brain injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 192-205"},"PeriodicalIF":3.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.molimm.2025.12.004
Qian Fang , Ruoxin Wang , Xiumei Liu , Yajun Wang , Qingping Xie , Chunyang Guo , Mingzhe Yuan , Xubo Wang
Hepcidins are a class of cysteine-rich antimicrobial peptides that exert significant impacts in response to a variety of pathogens. In this study, two hepcidins were identified from silver pomfret (Pampus argenteus), namely Pahepcidin1 and Pahepcidin2. Our findings revealed that Pahepcidin1 consists of a 267 open reading frame (ORF) encoding 91 amino acids, while Pahepcidin2 consists of 246 bp ORF encoding 81 amino acids. Sequence comparison between Pahepcidins and other homologous genes demonstrated the presence of eight conserved cysteines in the C-terminus region of Pahepcidin1 and six cysteine residues in the C-terminus region of Pahepcidin2. Phylogenetic analysis indicated that both Pahepcidin1 and Pahepcidin2 clustered with other fish homologues, respectively. The results of tissue-specific expression analysis showed that Pahepcidins exhibited the highest expression level in the liver; moreover, the expression level of Pahepcidin1 in silver pomfret liver cells (PaL cells) was also significantly increased after stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (poly I:C), and Staphylococcus aureus (S. aureus). Meanwhile, this study verified the antibacterial function of recombinant Pahepcidin1, and the results indicated that it possessed broad antibacterial activity against both Gram-positive bacteria (S. aureus) and Gram-negative bacteria (Edwardsiella tarda). In addition, the overexpression of Pahepcidin1 could significantly alter the transcriptional levels of key genes in the NF-κB pathway and downstream immune-related genes. In vivo validation via Vibrio parahaemolyticus challenge showed that Pahepcidin1 expression in silver pomfret liver was significantly upregulated at 3 h and peaked at 6 h, then downregulated to below the baseline from 12 h to 48 h. These results suggested that Pahepcidin1 might play an essential role in the innate immune system modulation of silver pomfret, providing valuable insights into understanding the antimicrobial immune mechanism of this species.
Hepcidins是一类富含半胱氨酸的抗菌肽，在对多种病原体的反应中发挥重要作用。本研究从银鲳鱼（Pampus argenteus）中鉴定出两种hepcidin，即Pahepcidin1和Pahepcidin2。结果表明，Pahepcidin1由267个开放阅读框（ORF）组成，编码91个氨基酸，而Pahepcidin2由246个 bp ORF组成，编码81个氨基酸。Pahepcidins与其他同源基因的序列比较表明，在Pahepcidin1的c端区存在8个保守的半胱氨酸，在Pahepcidin2的c端区存在6个半胱氨酸残基。系统发育分析表明，Pahepcidin1和Pahepcidin2分别与其他鱼类同源物聚集。组织特异性表达分析结果显示Pahepcidins在肝脏中表达量最高；此外，经脂多糖（LPS）、多肌苷-多胞酸（poly I:C）和金黄色葡萄球菌（S. aureus）刺激后，Pahepcidin1在鲳鱼肝细胞（PaL细胞）中的表达水平也显著升高。同时，本研究验证了重组Pahepcidin1的抑菌功能，结果表明其对革兰氏阳性菌（金黄色葡萄球菌）和革兰氏阴性菌（迟缓爱德华菌）均具有广泛的抑菌活性。此外，Pahepcidin1过表达可显著改变NF-κB通路关键基因及下游免疫相关基因的转录水平。通过副溶血性弧菌攻击的体内验证表明，Pahepcidin1在银鲳鱼肝脏中的表达在3 h时显著上调，在6 h时达到峰值，然后在12 h至48 h时下调至低于基线。这些结果提示Pahepcidin1可能在鲳鱼先天免疫系统调节中发挥重要作用，为了解该物种的抗菌免疫机制提供了有价值的见解。
{"title":"The genetic characteristics of Pahepcidin1 and Pahepcidin2 in silver pomfret (Pampus argenteus) and their antibacterial functions in innate immunity","authors":"Qian Fang , Ruoxin Wang , Xiumei Liu , Yajun Wang , Qingping Xie , Chunyang Guo , Mingzhe Yuan , Xubo Wang","doi":"10.1016/j.molimm.2025.12.004","DOIUrl":"10.1016/j.molimm.2025.12.004","url":null,"abstract":"<div><div>Hepcidins are a class of cysteine-rich antimicrobial peptides that exert significant impacts in response to a variety of pathogens. In this study, two hepcidins were identified from silver pomfret (<em>Pampus argenteus</em>), namely <em>Pahepcidin1</em> and <em>Pahepcidin2</em>. Our findings revealed that <em>Pahepcidin1</em> consists of a 267 open reading frame (ORF) encoding 91 amino acids, while <em>Pahepcidin2</em> consists of 246 bp ORF encoding 81 amino acids. Sequence comparison between <em>Pahepcidins</em> and other homologous genes demonstrated the presence of eight conserved cysteines in the C-terminus region of Pahepcidin1 and six cysteine residues in the C-terminus region of Pahepcidin2. Phylogenetic analysis indicated that both Pahepcidin1 and Pahepcidin2 clustered with other fish homologues, respectively. The results of tissue-specific expression analysis showed that <em>Pahepcidins</em> exhibited the highest expression level in the liver; moreover, the expression level of <em>Pahepcidin1</em> in silver pomfret liver cells (PaL cells) was also significantly increased after stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (poly I:C), and <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Meanwhile, this study verified the antibacterial function of recombinant Pahepcidin1, and the results indicated that it possessed broad antibacterial activity against both Gram-positive bacteria (<em>S. aureus</em>) and Gram-negative bacteria (<em>Edwardsiella tarda</em>). In addition, the overexpression of Pahepcidin1 could significantly alter the transcriptional levels of key genes in the NF-κB pathway and downstream immune-related genes. In vivo validation via <em>Vibrio parahaemolyticus</em> challenge showed that <em>Pahepcidin1</em> expression in silver pomfret liver was significantly upregulated at 3 h and peaked at 6 h, then downregulated to below the baseline from 12 h to 48 h. These results suggested that <em>Pahepcidin1</em> might play an essential role in the innate immune system modulation of silver pomfret, providing valuable insights into understanding the antimicrobial immune mechanism of this species.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 163-173"},"PeriodicalIF":3.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.molimm.2025.12.009
Jing Xiao , Yan Wang
Objectives
This study aims to explore whether isoimperatorin (ISOIM) regulates the malignant phenotype of T‑cell acute lymphoblastic leukemia (T-ALL) cells through the PI3K/AKT pathway and programmed cell death ligand-1 (PD-L1).
Methods
Through in vitro experiments, ISOIM on T-ALL cell proliferation and apoptosis was evaluated using the cell counting kit-8 and EdU assays, flow cytometry, and TUNEL staining. Network pharmacology, molecular docking, and functional enrichment analyses were conducted to analyze the underlying mechanisms of ISOIM. Changes in apoptosis-related proteins, PD-L1 protein, and PI3K/AKT pathway-related proteins were assessed by western blotting.
Results
ISOIM inhibited T-ALL cell proliferation, promoted apoptosis, decreased Bcl-2 levels, and increased C-caspase-3 and Bax levels. KEGG and GO enrichment analyses indicated that the overlapping targets between ISOIM and ALL were related to the PD-1 checkpoint and PI3K/AKT pathway. Molecular docking analysis showed good binding between ISOIM and PIK3CA (also known as PI3K). ISOIM reduced PD-L1, p-PI3K, p-AKT, and p-mTOR levels. Moreover, the PI3K/AKT pathway activator 740 Y-P reversed the inhibitory effect of ISOIM on PD-L1 expression and the malignant behavior of T-ALL cells.
Conclusions
ISOIM inhibited the malignant behavior of T-ALL cells and reduced PD-L1 levels by suppressing the PI3K/AKT pathway. This study provides a theoretical basis for developing novel treatment strategies for ALL.
{"title":"Isoimperatorin inhibits cell proliferation and induces apoptosis via regulating PI3K/AKT pathway in acute lymphoblastic leukemia","authors":"Jing Xiao , Yan Wang","doi":"10.1016/j.molimm.2025.12.009","DOIUrl":"10.1016/j.molimm.2025.12.009","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to explore whether isoimperatorin (ISOIM) regulates the malignant phenotype of T‑cell acute lymphoblastic leukemia (T-ALL) cells through the PI3K/AKT pathway and programmed cell death ligand-1 (PD-L1).</div></div><div><h3>Methods</h3><div>Through <em>in vitro</em> experiments, ISOIM on T-ALL cell proliferation and apoptosis was evaluated using the cell counting kit-8 and EdU assays, flow cytometry, and TUNEL staining. Network pharmacology, molecular docking, and functional enrichment analyses were conducted to analyze the underlying mechanisms of ISOIM. Changes in apoptosis-related proteins, PD-L1 protein, and PI3K/AKT pathway-related proteins were assessed by western blotting.</div></div><div><h3>Results</h3><div>ISOIM inhibited T-ALL cell proliferation, promoted apoptosis, decreased Bcl-2 levels, and increased C-caspase-3 and Bax levels. KEGG and GO enrichment analyses indicated that the overlapping targets between ISOIM and ALL were related to the PD-1 checkpoint and PI3K/AKT pathway. Molecular docking analysis showed good binding between ISOIM and PIK3CA (also known as PI3K). ISOIM reduced PD-L1, p-PI3K, p-AKT, and p-mTOR levels. Moreover, the PI3K/AKT pathway activator 740 Y-P reversed the inhibitory effect of ISOIM on PD-L1 expression and the malignant behavior of T-ALL cells.</div></div><div><h3>Conclusions</h3><div>ISOIM inhibited the malignant behavior of T-ALL cells and reduced PD-L1 levels by suppressing the PI3K/AKT pathway. This study provides a theoretical basis for developing novel treatment strategies for ALL.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 181-191"},"PeriodicalIF":3.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.molimm.2025.12.006
Hao Xiong, Zhu Shen
Background
Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN) induced by programmed cell death protein 1 (PD-1) inhibitors is a life-threatening condition. Although the exact pathogenesis remains unknown, its treatment mainly relies on high-dose systemic corticosteroids. Given the vital role of tumor necrosis factor-alpha (TNF-α) in classic SJS/TEN, this study sought to investigate the expression of TNF-α and evaluate the effectiveness and safety of combination therapy of etanercept and systemic corticosteroids in PD-1 inhibitor-induced SJS/TEN.
Methods
PD-1 inhibitor-induced SJS/TEN patients (n = 5) meeting diagnostic criteria, including skin biopsy-confirmed full-thickness epidermal necrosis with PD-1 as the sole culprit drug by ALDEN scoring, were enrolled in the study. Single-cell RNA sequencing (scRNA-seq) was conducted on lesional skin from one index patient (blister, erythema, and normal sites). Immunofluorescence staining for TNF-α was performed on samples from all five patients. Finally, a combination therapy of etanercept and systemic corticosteroids was administered to the patients, and the re-epithelization time, corticosteroid treatment duration, and prednisone cumulative dose were analyzed.
Results
scRNA-seq revealed significantly increased TNF-α expression in lesional skin compared with normal skin (p < 0.05), primarily from macrophages, which represented the predominant cell population in the lesion. Immunofluorescence confirmed TNF-α elevation in all five patients (p < 0.05). Besides, combination therapy resulted in rapid re-epithelialization (5.75 ± 1.48 days), a shorter steroid duration (17.75 ± 2.86 days), and reduced cumulative prednisone use (9.83 ± 3.71 mg/kg). No treatment-related severe adverse events occurred. One patient subsequently received a PD-1 inhibitor after recovery and tolerated the re-treatment without complication.
Conclusions
Our findings demonstrated upregulation of TNF-α expression in PD-1 inhibitor-induced SJS/TEN, mainly derived from macrophages. The combination of etanercept and systemic corticosteroids exhibits huge potential for treating this patient population.
{"title":"Increased TNF-α in SJS/TEN induced by PD-1 inhibitors supports the combination therapy of etanercept and systemic corticosteroids","authors":"Hao Xiong, Zhu Shen","doi":"10.1016/j.molimm.2025.12.006","DOIUrl":"10.1016/j.molimm.2025.12.006","url":null,"abstract":"<div><h3>Background</h3><div>Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN) induced by programmed cell death protein 1 (PD-1) inhibitors is a life-threatening condition. Although the exact pathogenesis remains unknown, its treatment mainly relies on high-dose systemic corticosteroids. Given the vital role of tumor necrosis factor-alpha (TNF-α) in classic SJS/TEN, this study sought to investigate the expression of TNF-α and evaluate the effectiveness and safety of combination therapy of etanercept and systemic corticosteroids in PD-1 inhibitor-induced SJS/TEN.</div></div><div><h3>Methods</h3><div>PD-1 inhibitor-induced SJS/TEN patients (n = 5) meeting diagnostic criteria, including skin biopsy-confirmed full-thickness epidermal necrosis with PD-1 as the sole culprit drug by ALDEN scoring, were enrolled in the study. Single-cell RNA sequencing (scRNA-seq) was conducted on lesional skin from one index patient (blister, erythema, and normal sites). Immunofluorescence staining for TNF-α was performed on samples from all five patients. Finally, a combination therapy of etanercept and systemic corticosteroids was administered to the patients, and the re-epithelization time, corticosteroid treatment duration, and prednisone cumulative dose were analyzed.</div></div><div><h3>Results</h3><div>scRNA-seq revealed significantly increased TNF-α expression in lesional skin compared with normal skin (<em>p</em> < 0.05), primarily from macrophages, which represented the predominant cell population in the lesion. Immunofluorescence confirmed TNF-α elevation in all five patients (<em>p</em> < 0.05). Besides, combination therapy resulted in rapid re-epithelialization (5.75 ± 1.48 days), a shorter steroid duration (17.75 ± 2.86 days), and reduced cumulative prednisone use (9.83 ± 3.71 mg/kg). No treatment-related severe adverse events occurred. One patient subsequently received a PD-1 inhibitor after recovery and tolerated the re-treatment without complication.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrated upregulation of TNF-α expression in PD-1 inhibitor-induced SJS/TEN, mainly derived from macrophages. The combination of etanercept and systemic corticosteroids exhibits huge potential for treating this patient population.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 174-180"},"PeriodicalIF":3.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.molimm.2025.12.008
Jin-Woo Kim , Hyeon Ji Lee , Pahn-Shick Chang , Jung Min Lee , Jin-Chul Kim
Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation and disruption of the skin barrier. It is normally treated using moisturizers and steroids; however, these are palliatives and do not serve as a therapy. Mesenchymal stem cells (MSCs) are tissue stem cells with immunomodulatory activities, and exosomes reflect the physiologies of producer cells. Therefore, the use of MSCs and exosomes with their immunomodulatory activities is emerging as a new method to treat AD. Here, we used cobalt chloride (CoCl2) to induce hypoxic conditioning, and tested the therapeutic efficacy of exosomes derived from CoCl2-treated MSCs in treating AD. In vitro, the exosomes derived from CoCl2-treated MSCs increased the proliferation of HaCaT cells and decreased inflammatory cytokine levels. In the oxazolone-induced chronic AD mouse model, the exosomes derived from CoCl2-treated MSCs reduced ear thickness, restored the skin barrier, and reduced immune cell infiltration and inflammatory markers. These data indicated that hypoxic conditioning induced by the CoCl2 treatment enhanced the therapeutic efficacy of exosomes derived from MSCs, suggesting that these exosomes can be used to alleviate the symptoms of AD. Given the current AD treatment landscape dominated by biologics and JAK inhibitors, our approach may serve as a steroid-sparing, biologic-agnostic adjunct or alternative, leveraging the safety and manufacturability of cell-free therapy.
{"title":"Hypoxic conditioning induced by CoCl2 enhanced the therapeutic effects of mesenchymal stem cell-derived exosomes on oxazolone-induced atopic dermatitis-like skin lesions in BALB/c mice","authors":"Jin-Woo Kim , Hyeon Ji Lee , Pahn-Shick Chang , Jung Min Lee , Jin-Chul Kim","doi":"10.1016/j.molimm.2025.12.008","DOIUrl":"10.1016/j.molimm.2025.12.008","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation and disruption of the skin barrier. It is normally treated using moisturizers and steroids; however, these are palliatives and do not serve as a therapy. Mesenchymal stem cells (MSCs) are tissue stem cells with immunomodulatory activities, and exosomes reflect the physiologies of producer cells. Therefore, the use of MSCs and exosomes with their immunomodulatory activities is emerging as a new method to treat AD. Here, we used cobalt chloride (CoCl<sub>2</sub>) to induce hypoxic conditioning, and tested the therapeutic efficacy of exosomes derived from CoCl<sub>2</sub>-treated MSCs in treating AD. <em>In vitro</em>, the exosomes derived from CoCl<sub>2</sub>-treated MSCs increased the proliferation of HaCaT cells and decreased inflammatory cytokine levels. In the oxazolone-induced chronic AD mouse model, the exosomes derived from CoCl<sub>2</sub>-treated MSCs reduced ear thickness, restored the skin barrier, and reduced immune cell infiltration and inflammatory markers. These data indicated that hypoxic conditioning induced by the CoCl<sub>2</sub> treatment enhanced the therapeutic efficacy of exosomes derived from MSCs, suggesting that these exosomes can be used to alleviate the symptoms of AD. Given the current AD treatment landscape dominated by biologics and JAK inhibitors, our approach may serve as a steroid-sparing, biologic-agnostic adjunct or alternative, leveraging the safety and manufacturability of cell-free therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 153-162"},"PeriodicalIF":3.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.molimm.2025.12.007
Dan Wan , Xiao Liang , Fanfan Liang , Mengchen Zhu , Chongyu Zhang , Shaoying Zhang
Background
Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for disseminated malignancies. However, ex vivo-expanded tumor-infiltrating lymphocytes (TIL) often rapidly progress to a state of functional exhaustion or suppression within the tumor microenvironment. Interleukin-7(IL-7) not only supports the survival of T-lymphocyte in vivo but also induces vigorous expansion of naïve and memory T lymphocytes in vitro. Upregulating the expression of interleukin-7 receptor alpha (IL-7Rα) helps T cells restore their responsiveness to IL-7 signaling, aids in their survival, and enables them to regain anti-tumor activity.
Methods
Firstly, we utilized databases to analyze the expression changes of CD127 in different tumor tissues, clarifying the correlation between its expression changes and patient prognosis. Subsequently, we collected clinical patient samples to validate the expression changes of CD127 in tumor-infiltrating T cells. We also simulated the tumor microenvironment through in vitro co-culture to explore the impact of tumor cells on the expression of CD127 on the surface of T cells. After then, we screened for miRNAs that are complementary to the sequence of the TATA box region in the CD127 promoter and employed a CD127 promoter driven dual-luciferase reporter system to identify the specific miRNA capable of upregulating CD127 expression. Finally, we analyzed the effects of miRNA-mediated upregulation of CD127 on T cell function.
Results
Bioinformatics analysis and clinical validation both confirmed decreased IL-7Rα expression in tumors. Moreover, in clinical samples, IL-7Rα and miR-3188 expression levels showed concordant changes and a positive correlation. miR-3188 can upregulate the expression level of IL-7Rα by specifically targeting the TATA-box region of CD127 promoter. Utilizing miR-3188 to upregulate IL-7Rα expression can facilitate T cell survival, promote the development of memory T cells and enhance the secondary response and tumor-killing capacity of T cells.
Conclusion
Our findings reveal a novel mechanism of IL-7Rα regulation and propose a potential strategy to improve the persistence and functionality of T cells for ACT.
{"title":"The role of miR-3188-mediated transcriptional activation of IL-7Rα in tumor immunotherapy research","authors":"Dan Wan , Xiao Liang , Fanfan Liang , Mengchen Zhu , Chongyu Zhang , Shaoying Zhang","doi":"10.1016/j.molimm.2025.12.007","DOIUrl":"10.1016/j.molimm.2025.12.007","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for disseminated malignancies. However, <em>ex vivo</em>-expanded tumor-infiltrating lymphocytes (TIL) often rapidly progress to a state of functional exhaustion or suppression within the tumor microenvironment. Interleukin-7(IL-7) not only supports the survival of T-lymphocyte <em>in vivo</em> but also induces vigorous expansion of naïve and memory T lymphocytes <em>in vitro</em>. Upregulating the expression of interleukin-7 receptor alpha (<em>IL-7Rα</em>) helps T cells restore their responsiveness to <em>IL-7</em> signaling, aids in their survival, and enables them to regain anti-tumor activity.</div></div><div><h3>Methods</h3><div>Firstly, we utilized databases to analyze the expression changes of <em>CD127</em> in different tumor tissues, clarifying the correlation between its expression changes and patient prognosis. Subsequently, we collected clinical patient samples to validate the expression changes of <em>CD127</em> in tumor-infiltrating T cells. We also simulated the tumor microenvironment through <em>in vitro</em> co-culture to explore the impact of tumor cells on the expression of <em>CD127</em> on the surface of T cells. After then, we screened for miRNAs that are complementary to the sequence of the TATA box region in the <em>CD127</em> promoter and employed a <em>CD127</em> promoter driven dual-luciferase reporter system to identify the specific miRNA capable of upregulating <em>CD127</em> expression. Finally, we analyzed the effects of miRNA-mediated upregulation of <em>CD127</em> on T cell function.</div></div><div><h3>Results</h3><div>Bioinformatics analysis and clinical validation both confirmed decreased <em>IL-7Rα</em> expression in tumors. Moreover, in clinical samples, <em>IL-7Rα</em> and <em>miR-3188</em> expression levels showed concordant changes and a positive correlation. <em>miR-3188</em> can upregulate the expression level of <em>IL-7Rα</em> by specifically targeting the TATA-box region of <em>CD127</em> promoter. Utilizing <em>miR-3188</em> to upregulate <em>IL-7Rα</em> expression can facilitate T cell survival, promote the development of memory T cells and enhance the secondary response and tumor-killing capacity of T cells.</div></div><div><h3>Conclusion</h3><div>Our findings reveal a novel mechanism of <em>IL-7Rα</em> regulation and propose a potential strategy to improve the persistence and functionality of T cells for ACT.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 142-152"},"PeriodicalIF":3.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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