Free Radical Biology and Medicine最新文献

{"title":"Quantitative spatial visualization of X-ray irradiation via redox reaction by dynamic nuclear polarization magnetic resonance imaging","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.278","DOIUrl":"10.1016/j.freeradbiomed.2024.10.278","url":null,"abstract":"<div><div>The dose of X-ray irradiation is commonly measured by point assessment with an ionization chamber dosimeter. However, to achieve spatially accurate delivery of X-ray to avoid the exposure to normal tissues, an accurate imaging method for spatially and quantitatively detecting exposure is required. Herein, we present a novel method to visualize X-ray exposure using low-field dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) with nitroxyl radical tempol as the chemical dosimeter. In this system, gel phantoms containing glutathione (GSH) and the paramagnetic tempol radical were used to monitor the deposited X-ray-irradiation via the redox reaction. The tempol radical level was evaluated by DNP-MRI whose signal intensity was linearly correlated with the radical concentration. The radical level in the presence of GSH decreased in proportion to the dose of X-irradiation deposited. In an imaging experiment simulating clinical radiotherapy, we used a clinical linear accelerator with a radiotherapy planning software to confirm the utility of the exposure imaging. The X-ray exposure and its distribution were clearly visualized on the gel phantom image acquired by DNP-MRI. The results were consistent with those specified in the radiotherapy plan where the intensity of the radiation beam was modulated. This exposure estimation will be useful for determining an accurate irradiation field and reducing off-target exposure in clinical settings<strong>.</strong></div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445778","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}

{"title":"2-Acetylacteoside improves recovery after ischemic stroke by promoting neurogenesis via the PI3K/Akt pathway","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.268","DOIUrl":"10.1016/j.freeradbiomed.2024.10.268","url":null,"abstract":"<div><div>Ischemic stroke induces adult neurogenesis in the subventricular zone (SVZ), even in elderly patients. Harnessing of this neuroregenerative response presents the therapeutic potential for post-stroke recovery. We found that phenylethanoid glycosides (PhGs) derived from <em>Cistanche deserticola</em> aid neural repair after stroke by promoting neurogenesis. Among these, 2-acetylacteoside had the most potent on the proliferation of neural stem cells (NSCs) <em>in vitro</em>. Furthermore, 2-acetylacteoside was shown to alleviate neural dysfunction by increase neurogenesis both <em>in vivo</em> and <em>in vitro</em>. RNA-sequencing analysis highlighted differentially expressed genes within the PI3K/Akt signaling pathway. The candidate target Akt was validated as being regulated by 2-acetylacteoside, which, in turn, enhanced the proliferation and differentiation of cultured NSCs after oxygen-glucose deprivation/reoxygenation (OGD/R), as evidenced by Western blot analysis. Subsequent analysis using cultured NSCs from adult subventricular zones (SVZ) confirmed that 2-acetylacteoside enhanced the expression of phosphorylated Akt (p-Akt), and its effect on NSC neurogenesis was shown to be dependent on the PI3K/Akt pathway. In summary, our findings elucidate for the first time the role of 2-acetylacteoside in enhancing neurological recovery, primarily by promoting neurogenesis via Akt activation following ischemic brain injury, which offers a novel strategy for long-term cerebrological recovery in ischemic stroke.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461757","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}

{"title":"Development of novel dual-target drugs against visceral leishmaniasis and combinational study with miltefosine","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.257","DOIUrl":"10.1016/j.freeradbiomed.2024.10.257","url":null,"abstract":"<div><div>The dual-target inhibitors (ZINC000008876351 and ZINC000253403245) were identified by utilizing an advanced computational drug discovery method by targeting two critical enzymes such as FeSODA (Iron superoxide dismutase) and TryR (Trypanothione reductase) within the antioxidant defense system of <em>Leishmania donovani</em> (<em>Ld</em>). <em>In vitro</em> enzyme inhibition kinetics reveals that both the compound's ability to inhibit the function of enzyme <em>Ld</em>FeSODA and <em>Ld</em>TryR with inhibition constant (Ki) value in the low μM range. Flow cytometry analysis, specifically at IC₅₀ and 2X IC₅₀ doses of both the compounds, the intracellular ROS was significantly increased as compared to the untreated control. The compounds ZINC000253403245 and ZINC000008876351 exhibited strong anti-leishmanial activity in a dose-dependent manner against both the promastigote and amastigote stages of the parasite. The data indicate that these molecules hold promise as potential anti-leishmanial agents for developing new treatments against visceral leishmaniasis, specifically targeting the LdFeSODA and LdTryR enzymes. Additionally, the <em>in vitro</em> MTT assay shows that combining these compounds with miltefosine produces a synergistic effect compared to miltefosine alone. This suggests that the compounds can boost miltefosine's effectiveness by synergistically inhibiting the growth of <em>L. donovani</em> promastigotes. Given the emergence of miltefosine resistance in some <em>Leishmania</em> strains, these findings are particularly significant.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399852","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}

{"title":"Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.273","DOIUrl":"10.1016/j.freeradbiomed.2024.10.273","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Subarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored. Ferroptosis, iron-dependent programmed cell death, has recently been shown to contribute to EBI. We aimed to investigate the effects of GPR4 inhibition on neurological deficits and neuronal ferroptosis after SAH in rats.</div></div><div><h3>Methods</h3><div>A total 253 Sprague Dawley (SD) male rats (weighing 275-330g) were utilized in this study. SAH was induced by endovascular perforation. NE-52-QQ57 (NE), a selective antagonist of GPR4 was administered intraperitoneally 1-hour post-SAH. To explore the mechanisms, RhoA activator U-46619 and YAP activator PY-60 were delivered intracerebroventricularly. Short- and long-term neurobehavior, SAH grading, western blot assay, ELISA assay, immunofluorescence staining, and transmission electron microscopy was performed post-SAH.</div></div><div><h3>Results</h3><div>Following SAH, there was an upregulation of GPR4 expression in neurons. GPR4 inhibition by NE improved both short-term and long-term neurological outcomes post-SAH. NE also reduced neuronal ferroptosis, as evidenced by decreased lipid peroxidation products 4HNE and MDA levels in brain tissues, and reduced mitochondrial shrinkage, increased mitochondria crista and decreased membrane density. The application of either U-46619 or PY-60 partially offset the neuroprotective effects of NE on neuronal ferroptosis in SAH rats.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that acid-sensing receptor GPR4 contributed to neuronal ferroptosis after SAH via RhoA/YAP pathway, and NE may be a potential therapeutic strategy to attenuate GPR4 mediated neuronal ferroptosis and EBI after SAH.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Race Within a Race: Starting Together, Finishing Apart.","authors":"Louise M Burke, Jamie Whitfield, John A Hawley","doi":"10.1016/j.freeradbiomed.2024.10.277","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2024.10.277","url":null,"abstract":"<p><p>Every four years the world's best athletes come together to compete in the Olympic games, electrifying audiences with incredible feats of speed, strength, endurance and skill as personal best performances and new records are set. However, the exceptional talent that underpin such performances is incomprehensible to most casual observers who often cannot appreciate how unique these athletes are. In this regard, endurance running, specifically the marathon, a 42.195 km foot race, provides one of the few occasions in sport outside of Olympic, world and national competitions, that permits sport scientists and fans alike to directly compare differences in the physiology between recreational and elite competitors. While these individuals may all cover the same distance, on the same course, on the same day - their experience and the physiological and psychological demands placed upon them are vastly different. There is, in effect, a \"race within a race\". In the current review we highlight the superior physiology of the elite endurance athlete, emphasizing the gap between elite competitors and well-trained, but less genetically endowed athletes. We draw attention to a range of inconsistencies in how current sports science practices are understood, implemented, and communicated in terms of the elite and not-so-elite endurance athlete.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461742","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}

{"title":"APEX1 in intestinal epithelium triggers neutrophil infiltration and intestinal barrier damage in ulcerative colitis","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.260","DOIUrl":"10.1016/j.freeradbiomed.2024.10.260","url":null,"abstract":"<div><div>Ulcerative colitis (UC) can lead to the generation of large amounts of reactive oxygen species and DNA damage. DNA repair caused by base excision repair (BER) enzymes is an important mechanism for maintaining genomic integrity. However, the specific relationship between the function of BER enzymes and UC remains unclear. To address this, we conducted a study on non-cancerous colon tissue from patients with UC, focusing on the role of apurinic/apyrimidinic endonuclease 1 (APEX1) in BER to explore its significance in the progression of UC. Our research found that the expression of APEX1 in epithelium cells was significantly correlated to the severity of inflammatory bowel disease (IBD) and the infiltration and function of neutrophils in human UC and mouse models, particularly in relation to neutrophil extracellular traps (NETs) and the degranulation processes. APEX1 deficiency resulted in decreased production of the chemokines CXCL1 by the NF-κB pathway in epithelium cells, leading to reduced accumulation and activation of neutrophils associated with colitis in colon tissue, as well as decreased levels of IL-1β. Furthermore, APEX1 deficiency reduced symptoms of colitis by decreasing epithelial cell apoptosis and altering the gut microbiome. Studies related to the redox activity of APEX1 have shown that the combination of the redox inhibitor E3330 with 5-aminosalicylic acid (5-ASA) can effectively alleviate colitis, indicating that APEX1 has promising prospects for clinical treatment of IBD. APEX1 is required for interactions between neutrophil and intestinal epithelial cells. This study provided a mechanism demonstrating that APEX1 protein triggered the risk of UC by promoting neutrophil infiltration and compromising intestinal epithelial barrier function.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399849","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}

{"title":"FUNDC1-mediated mitophagy regulates photodamage independently of the PINK1/Parkin-dependent pathway","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.272","DOIUrl":"10.1016/j.freeradbiomed.2024.10.272","url":null,"abstract":"<div><h3>Background</h3><div>Ultraviolet B(UVB) triggers a pro-survival response through mitophagy, but the role of FUNDC1-mediated mitophagy in photodamaged skin remains unexplored.</div></div><div><h3>Objectives</h3><div>To clarify the function of mitophagy in UVB-induced photodamaged skin.</div></div><div><h3>Methods</h3><div>To investigate the role of FUNDC1-mediated mitophagy in UVB-induced mitochondrial damage and cell apoptosis, FUNDC1 knockdown in C57BL/6 mice was performed using adeno-associated virus. Additionally, FUNDC1 overexpression and knockdown in HaCaT cells were conducted using lentivirus. A comprehensive analysis was conducted on a panel of human sun-exposed skin samples, alongside control samples, to assess the expression levels of FUNDC1.</div></div><div><h3>Results</h3><div>In UVB-induced C57BL/6 mice, the dorsal skin showed photodamage including erythema, scaling, erosion, and scabs. The expression levels of PINK1, Parkin, and BNIP3 did not show significant changes, while FUNDC1 expression consistently declined along with LC3B. Cytochrome C, Bax, and cleaved-caspase3 were upregulated, while Bcl2 was downregulated. UVB-induced HaCaT cells showed mitochondrial damage, accompanied by FUNDC1 downregulation and BNIP3 upregulation, while PINK1 and Parkin showed no significant changes. FUNDC1 overexpression led to an increase in mtROS and a decrease in mitochondrial membrane potential and ATP levels, indicating complete mitochondrial clearance and exacerbated cell death. FUNDC1 knockdown protected against UVB-induced photodamage in mice and mitigated mitochondrial damage and apoptosis in HaCaT cells by activating compensatory PINK1/Parkin-dependent mitophagy, which was evidenced by upregulation of PINK1 and Bcl2 and downregulation of Bax. In human sun-exposed skin samples, there was a decrease in the number of FUNDC1⁺ cells compared with non-sun-exposed controls.</div></div><div><h3>Conclusions</h3><div>FUNDC1-mediated mitophagy regulates skin photodamage and provides a novel mechanism for resisting photodamage, presenting a potential target for future therapeutic interventions.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399850","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}

{"title":"Nitrosyl Hemoglobin Formation from Nitrite in Normal and Sickle Blood","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.271","DOIUrl":"10.1016/j.freeradbiomed.2024.10.271","url":null,"abstract":"<div><div>Sickle cell anemia is caused by a single mutation in the gene encoding the beta subunit of hemoglobin. Due to this mutation, sickle cell hemoglobin (HbS) polymerizes under hypoxic conditions, decreasing red blood cell deformability and leading to multiple pathological effects that cause substantial morbidity and mortality. Several pre-clinical and human studies have demonstrated that the anion nitrite has potential therapeutic benefits for patients with sickle cell disease. Nitrite is reduced to nitric oxide (NO) by deoxygenated hemoglobin contributing to vasodilation, decreasing platelet activation, decreasing cellular adhesion to activated endothelium, and decreasing red cell hemolysis; all of which could ameliorate patient morbidities. Previous work on extracellular hemoglobin has shown that solution phase HbS reduces nitrite to NO faster than normal adult hemoglobin (HbA), while polymerized HbS reduces nitrite slower than HbA. In this work, we compared the rate of nitrite reduction to NO measured by the formation of nitrosyl hemoglobin in sickle and normal red blood cells at varying hemoglobin oxygen saturations. We found the overall rate of nitrite reduction between normal and sickle red blood cells was similar and confirmed this result under partially oxygenated conditions, but normal red blood cells reduced nitrite faster than sickle red blood cells under anoxia where HbS polymerization is maximal. These results are consistent with previous work using extracellular hemoglobin where the rate of reduction by solution phase HbS makes up for the slower reduction by polymer phase HbS under partially oxygenated conditions, but the polymer phase kinetics dominates in the complete absence of oxygen.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399851","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}

{"title":"SGLT1 inhibition alleviates radiation-induced intestinal damage through promoting mitochondrial homeostasis","authors":"","doi":"10.1016/j.freeradbiomed.2024.10.274","DOIUrl":"10.1016/j.freeradbiomed.2024.10.274","url":null,"abstract":"<div><div>Radiation-induced intestinal injury (RIII) constitutes a challenge in radiotherapy. Ionizing radiation (IR) induces DNA and mitochondrial damage by increasing reactive oxygen species (ROS). Sodium–glucose cotransporter 1 (SGLT1) is abundant in the gastrointestinal tract and the protective effects of inhibited SGLT1 in kidney and cardiovascular disease have been widely reported. However, the function of SGLT1 in RIII remains unclear. Herein, we reported that IR induced intestinal epithelial cell damage along with upregulation of SGLT1 in vivo and in vitro, which was alleviated by inhibition of SGLT1. Specifically, maintaining intestinal cell homeostasis was detected through cellular proliferation, apoptosis, and DNA damage assays, promoting epithelial regeneration and lifespan extension. Considering the importance of mitochondrial function in cell fate, we next confirmed that SGLT inhibition maintains mitochondrial homeostasis through enhanced mitophagy in intestinal epithelial cells. Finally, based on the bioinformatics analysis and cell validation, we demonstrated that inhibition of SGLT1 suppresses the PI3K/AKT/mTOR pathway to enhance mitophagy activation post-irradiation. In addition, we preliminarily demonstrate that SGLT inhibitors do not affect the radiosensitivity of tumors. Hence, our findings suggest that inhibition of SGLT is a promising therapeutic strategy to protect against RIII. To the best of our knowledge, this is the first report on the potential effect of SGLT1 inhibition in RIII.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406316","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}

{"title":"Clerodane diterpene 3-deoxycaryoptinol (Clerodin) selectively induces apoptosis in human monocytic leukemia (THP-1) cells and upregulates apoptotic protein caspase-3.","authors":"Bharathkumar Nagaraj, Arvind Sivasubramanian, Shazia Anjum Musthafa, Sadiq Muhammad, Aswathy Karanath Anilkumar, Ganesh Munuswamy-Ramanujam, Chinnaperumal Kamaraj, Sivaraman Dhanasekaran, Vetriselvan Subramaniyan","doi":"10.1016/j.freeradbiomed.2024.10.275","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2024.10.275","url":null,"abstract":"<p><p>3-deoxycaryoptinol (Clerodin) is a clerodane diterpene isolated from the leaves of Clerodendrum infortunatum. The present research investigates the anticancer therapeutic efficacy of clerodin in human monocytic leukemic (THP-1) cells for the first time. In vitro assay using THP-1 cells showed the cytotoxic ability of clerodin. Further, Annexin-V(FITC)/PI and intracellular ROS (DCFDA) assays carried out using flow cytometry, and confocal laser scanning microscopy confirmed the apoptotic potential of clerodin. Moreover, the western blot was used to detect mitochondrial apoptosis of THP-1 cells. RT-PCR, ELISA, and western blot analysis clearly indicated that clerodin significantly increased the expression of pro-apoptotic marker caspase-3 in THP-1 cells. clerodin also selectively targeted the G2/M phase of THP-1 cells, a key feature for anticancer molecules. Importantly, the clerodin did not exhibit cytotoxicity against human peripheral blood cells. These properties of clerodin make it a potential chemotherapeutic agent that can selectively induce apoptosis in leukemia-like cancer cells.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406314","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}