Bioorganic & Medicinal Chemistry最新文献

Oxidative complexity: The role of ROS in the tumor environment and therapeutic implications 氧化复杂性：ROS在肿瘤环境中的作用及其治疗意义

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-15 DOI: 10.1016/j.bmc.2025.118241

Tingfeng Shen , Yutong Wang , Linmao Cheng , Ann M. Bode , Ya Gao , Shuntong Zhang , Xue Chen , Xiangjian Luo

{"title":"Oxidative complexity: The role of ROS in the tumor environment and therapeutic implications","authors":"Tingfeng Shen , Yutong Wang , Linmao Cheng , Ann M. Bode , Ya Gao , Shuntong Zhang , Xue Chen , Xiangjian Luo","doi":"10.1016/j.bmc.2025.118241","DOIUrl":"10.1016/j.bmc.2025.118241","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) constitutes a group of reactive molecules that play a critical role in biological processes. Varying ROS levels have been frequently observed in cancer cells and the tumor microenvironment (TME). The role of ROS displays significant complexity in cancer development and therapy. Elevated ROS levels can induce metabolic reprogramming and promote the proliferation, invasion, and metastasis of cancer cells, resulting in cancer progression. However, excessive ROS accumulation leads to the occurrence of apoptosis, pyroptosis, necroptosis, and ferroptosis in cancer cells, which restrains tumor development. In the TME, ROS frequently promotes angiogenesis and remodels the extracellular matrix (ECM) by enhancing the differentiation of cancer-associated fibroblasts (CAFs), thereby supporting tumor growth. Concurrently, high ROS levels favour immunosuppressive cells, including M2-polarized macrophages, and regulatory T cells (Tregs), while impairing the antitumor capabilities of T cells. In the aspect of cancer therapy, it is overly simplistic to merely combine chemoradiotherapy with antioxidants as a therapeutic strategy. Instead, highlighting targeted therapies that modulate ROS is essential, given their inherent complexity. Fortunately, a variety of innovative treatments have emerged, including nanodrug delivery systems (NDDS), proteolysis-targeting chimeras (PROTAC), and adoptive cell therapy (ADT), which not only exhibit synergistic effects with immune checkpoint therapy (ICT), but also enhance the antitumor capabilities of the TME. In this paper, we elucidate the mechanism of ROS production, enumerate the role of ROS in cancer development and the TME, and discuss advancements in ROS-targeted cancer therapeutics.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118241"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070185","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}

引用次数: 0

Advances in cancer immunotherapy using small-molecular inhibitors targeting the PD-1/PD-L1 interaction

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-12 DOI: 10.1016/j.bmc.2025.118238

Feng Zhang , Sivaramakarthikeyan Ramar , Yu Wang , Haoran Xu , Koutian Zhang , Annoor Awadasseid , Guowu Rao , Wen Zhang

{"title":"Advances in cancer immunotherapy using small-molecular inhibitors targeting the PD-1/PD-L1 interaction","authors":"Feng Zhang , Sivaramakarthikeyan Ramar , Yu Wang , Haoran Xu , Koutian Zhang , Annoor Awadasseid , Guowu Rao , Wen Zhang","doi":"10.1016/j.bmc.2025.118238","DOIUrl":"10.1016/j.bmc.2025.118238","url":null,"abstract":"<div><div>Cancer cells evade immune responses by interacting with PD-1 and its ligand, PD-L1. Although monoclonal antibodies targeting this pathway have revolutionized oncology, their high production costs, poor oral bioavailability, and limited tumor penetration remain significant challenges. Small-molecule inhibitors provide a promising alternative, offering advantages such as improved tumor penetration and cost-effectiveness. This review highlights advancements in small-molecule PD-1/PD-L1 inhibitors, focusing on their mechanisms, structural designs, and therapeutic potential. Key innovations, including biphenyl scaffolds, heterocyclic frameworks, enhance binding efficiency and immune activation. The article effectively integrates fundamental principles of drug chemistry with real-world clinical needs, offering a comprehensive approach to the design of PD-1/PD-L1 small-molecule inhibitors. It systematically classifies various molecular structures, analyzes relevant industrial cases, and incorporates the most recent research findings. By examining these aspects, it uncovers the underlying logic driving the design process and provides a fresh, innovative perspective on advancing the field of immune small-molecule inhibitors for cancer therapy.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118238"},"PeriodicalIF":3.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943518","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}

引用次数: 0

Lectin-mediated adhesion: Testing of tailor-made cellulose derivatives with ConA and live E. coli bacteria 凝集素介导的粘附：用ConA和活大肠杆菌定制的纤维素衍生物的测试

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-08 DOI: 10.1016/j.bmc.2025.118236

Carina Spormann , Tobias Dorn , Stefan Schwaiger , Sönke Sdunnus , Andreas Koschella , Hanspeter Kählig , Thomas Heinze , Thisbe K. Lindhorst , Tanja M. Wrodnigg

{"title":"Lectin-mediated adhesion: Testing of tailor-made cellulose derivatives with ConA and live E. coli bacteria","authors":"Carina Spormann , Tobias Dorn , Stefan Schwaiger , Sönke Sdunnus , Andreas Koschella , Hanspeter Kählig , Thomas Heinze , Thisbe K. Lindhorst , Tanja M. Wrodnigg","doi":"10.1016/j.bmc.2025.118236","DOIUrl":"10.1016/j.bmc.2025.118236","url":null,"abstract":"<div><div>Due to the high exigence for treatment of bacterial infections, anti-adhesion therapy has emerged as an alternative method in an era of antibiotic resistance. Here, we have conjugated azido-functionalized cellulose with specific carbohydrate ligands (mannose and glucose, respectively) via copper-catalyzed azide-alkyne click chemistry (CuAAC) resulting in homo- and hetero-glycosylated cellulose derivatives with a DS > 0.9. The new materials, Cellul<sup>Man</sup> and Cellul<sup>ManGlc</sup>, were evaluated as potential anti-adhesive reagents with type 1-fimbriated <em>E. coli</em> bacteria and additionally with the plant lectin Concanavalin A (ConA). We have determined the adhesion properties of the new glycopolymers as well as their agglutination behavior in an in-depth study combining two- and three-dimensional assays. The tested synthetic glycopolymers differ in their biological behavior as lectin ligands depending on the respective glycodecoration. In particular, Cellul<sup>Man</sup> shows a remarkably low minimal effective concentration c<sub>min</sub> ≤ 2 pg/mL as adhesive material with <em>E. coli</em>. Overall, the assays demonstrate that glyco-modified cellulose serves as an excellent antiadhesive as well as adhesive surface material for both type 1 fimbriated <em>E. coli</em> and ConA, being superior to natural polysaccharides.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118236"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935460","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}

引用次数: 0

Discovery of novel β-carboline/melatonin hybrids as STAT3 inhibitors for the treatment of lung cancer via increasing DNA damage 发现新的β-碳碱/褪黑素杂交体作为STAT3抑制剂，通过增加DNA损伤治疗肺癌

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-06 DOI: 10.1016/j.bmc.2025.118227

Xiaojuan Yang , Shuting Jia , Chao Xia , Yuping Yang

引用次数: 0

Development of Carprofen analogues with activity against Mycobacterium tuberculosis 抗结核分枝杆菌卡洛芬类似物的研制

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-06 DOI: 10.1016/j.bmc.2025.118226

Liam T. Martin , Chris Daniel , Marcus Guldberg-Allen , Anushandan Navaratnarajah , Silvia Anselmi , Tina-Maria D. Burova , Sam Willcocks , Helen C. Hailes , Sanjib Bhakta

引用次数: 0

The new N2-phenyl-N4-5-(dimethylphosphinyl)-6-quinoxalinamine pyrimidine-2,4-diamine derivatives as EGFR inhibitors to overcome C797S-mediated resistance 新的n2 -苯基- n4 -5-（二甲基膦酰）-6-喹啉胺嘧啶-2,4-二胺衍生物作为EGFR抑制剂克服c797s介导的耐药性

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-05 DOI: 10.1016/j.bmc.2025.118224

Jiadai Liu , Jiaqi Qiu , Chunlong Wang , Haoran Nie , Mengxuan Wang , Shuai Zhang , Fangyi Jia , Xianping Dai , Baijiao An

{"title":"The new N2-phenyl-N4-5-(dimethylphosphinyl)-6-quinoxalinamine pyrimidine-2,4-diamine derivatives as EGFR inhibitors to overcome C797S-mediated resistance","authors":"Jiadai Liu , Jiaqi Qiu , Chunlong Wang , Haoran Nie , Mengxuan Wang , Shuai Zhang , Fangyi Jia , Xianping Dai , Baijiao An","doi":"10.1016/j.bmc.2025.118224","DOIUrl":"10.1016/j.bmc.2025.118224","url":null,"abstract":"<div><div>A series of novel <em>N</em><sup>2</sup>-phenyl-<em>N</em><sup>4</sup>-5-(dimethylphosphinyl)-6-quinoxalinaminepyrimidine-2,4-diamine derivatives were synthesized and evaluated as potential inhibitors of EGFR C797S-mediated resistance. Notably, most of these compounds exhibited robust antiproliferative activity against Baf3-EGFR<sup>L858R/T790M/C797S</sup> and Baf3-EGFR<sup>Del19/T790M/C797S</sup> cancer cell lines with IC<sub>50</sub> values in the nanomolar range. Among them, compound <strong>Y9m</strong> showed the most potent inhibitory activity with IC<sub>50</sub> values as low as 8–9 nM. Mechanistic studies showed that <strong>Y9m</strong> effectively inhibited EGFR <sup>L858R/T790M/C797S</sup> and EGFR<sup>Del19/T790M/C797S</sup> kinases, which modulate the phosphorylation of the EGFR signaling pathway proteins. Notably, PI3K phosphorylation in the mTOR signaling pathway decreased as compound concentration increased, which implies that <strong>Y9m</strong> enhances anti-tumor activity by blocking the phosphorylation of the dual signaling pathways. <strong>Y9m</strong> induced cell cycle arrest at the G0/G1 phase by inducing apoptosis through the inhibition of CyclinD1 expression and regulating Caspase-3 expression. In conclusion, <strong>Y9m</strong> is a promising candidate in the development of highly efficacious anticancer agents.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118224"},"PeriodicalIF":3.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918555","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}

引用次数: 0

Screening and evaluation of hydrophobic cell-penetrating peptides for antisense oligonucleotide delivery 反义寡核苷酸递送用疏水细胞穿透肽的筛选与评价

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-03 DOI: 10.1016/j.bmc.2025.118223

Saki Tamura , Genichiro Tsuji , Yosuke Demizu

{"title":"Screening and evaluation of hydrophobic cell-penetrating peptides for antisense oligonucleotide delivery","authors":"Saki Tamura , Genichiro Tsuji , Yosuke Demizu","doi":"10.1016/j.bmc.2025.118223","DOIUrl":"10.1016/j.bmc.2025.118223","url":null,"abstract":"<div><div>Antisense oligonucleotides (ASOs) are promising therapeutic agents targeting intracellular RNA, yet their clinical application is limited by poor membrane permeability. To overcome this challenge, we investigated hydrophobic cell-penetrating peptides (CPPs) as alternative delivery vectors. Ten hydrophobic CPPs were synthesized and screened for cellular uptake using live-cell fluorescence imaging. Selected CPPs were conjugated to a chemically modified ASO via click chemistry, and their intracellular delivery and antisense efficacy were evaluated using a splicing reporter assay in HeLa 705 cells. While certain CPPs, such as <strong>MPG</strong>, showed high membrane permeability, conjugation with ASOs did not always translate to enhanced antisense activity. Notably, among the evaluated CPP-ASO conjugates, <strong>SP-ASO</strong> exhibited the most potent functional activity despite moderate uptake. This finding suggests that factors beyond membrane permeability, such as endosomal escape, intracellular trafficking, or nuclear delivery efficiency, may critically influence the overall efficacy. Fluorescence microscopy confirmed lysosomal entrapment of both naked and CPP-conjugated ASOs. These findings emphasize the importance of rational design strategies that address endosomal release to maximize the therapeutic potential of CPP-ASO conjugates.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118223"},"PeriodicalIF":3.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908302","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}

引用次数: 0

Discovery of new protein partners of anterior gradient 2 (AGR2) from cell-cell adhesion pathway using genetically-encoded photo-crosslinker DiZPK 利用遗传编码的光交联剂DiZPK发现细胞-细胞粘附途径中前梯度2 （AGR2）的新蛋白伴侣

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-03 DOI: 10.1016/j.bmc.2025.118225

Shafi Ullah , Siva Bharath Merugu , Shiyao Chen , Yaxue Zhao , Dawei Li , Huchen Zhou

{"title":"Discovery of new protein partners of anterior gradient 2 (AGR2) from cell-cell adhesion pathway using genetically-encoded photo-crosslinker DiZPK","authors":"Shafi Ullah , Siva Bharath Merugu , Shiyao Chen , Yaxue Zhao , Dawei Li , Huchen Zhou","doi":"10.1016/j.bmc.2025.118225","DOIUrl":"10.1016/j.bmc.2025.118225","url":null,"abstract":"<div><div>Anterior gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers including breast, prostate, and lung cancers. Thus, there have been great efforts to unveil the roles of AGR2 as an extracellular signaling molecule and intracellular endoplasmic reticulum (ER) chaperone. However, it remains challenging to capture the whole protein interactome of AGR2 because both weak and transient interacting partners tend to be washed off during purification. In order to capture weak and transient interacting protein partners, a genetically-encoded photo-crosslinker, DiZPK (3-(3-methyl-3H-diazirine-3-yl)-propaminocarbonyl-N<sup>ε</sup>-<span>l</span>-lysine), was introduced at the essential domains of AGR2. Photo-crosslinking reaction of the recombinant mutant AGR2<sup>Q85DiZPK</sup> was subsequently initiated by UV light (365 nm) in MCF-7 breast cancer cell lysate. After purification and further analysis by LC-MS/MS, we identified a number of AGR2 partner proteins that are involved in the cell–cell adhesion pathway. Namely, they are desmosomes-related proteins including γ-catenin, desmocollin-1 (DSC-1), desmoglein-1 (DSG-1), desmoplakin (DSP), and plakophillin-1 (PKP-1). Further protein–protein interaction studies, including immunofluorescence and molecular dynamic simulation analysis, especially using γ-catenin as an example, corroborated with the observation that AGR2 directly interacts with γ-catenin. We believe the identification of these new protein partners would help to unveil how AGR2 renders its roles in cell adhesion, migration, and ultimately metastasis of cancers, and these proteins are worthy of future in-depth study for the elucidation of AGR2-mediated cellular functions.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118225"},"PeriodicalIF":3.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935459","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}

引用次数: 0

Apoptosis induction by ceramide derivatives and its potential mechanisms through domain formation 神经酰胺衍生物诱导细胞凋亡及其结构域形成的潜在机制

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-02 DOI: 10.1016/j.bmc.2025.118222

Koya Tsujimura , Miho Yakabe , Hideaki Kano , Nobuaki Matsumori

{"title":"Apoptosis induction by ceramide derivatives and its potential mechanisms through domain formation","authors":"Koya Tsujimura , Miho Yakabe , Hideaki Kano , Nobuaki Matsumori","doi":"10.1016/j.bmc.2025.118222","DOIUrl":"10.1016/j.bmc.2025.118222","url":null,"abstract":"<div><div>Ceramides, which are recognized as pivotal signaling agents in cell differentiation and proliferation, elicit apoptosis in response to anticancer drugs and stress. Although the 1-hydroxy group of ceramide is considered to play an important role in inducing apoptosis, the detailed mechanism underlying ceramide-induced apoptosis remains elusive. We previously synthesized ceramide derivatives by transforming the 1-hydroxy group into amino and carboxy groups, and assessed their ability to form domains in artificial membranes. In this study, we evaluated the apoptotic activities of these derivatives against living cells. Surprisingly, despite the lack of the 1-hydroxy group, most of the derivatives exhibited apoptotic activity, with some being more active than ceramide. Confocal microscopy using fluorescent-ceramide and coherent anti-Stokes Raman scattering microscopy utilizing deuterated ceramide suggested the formation of large domains on living cell membranes. These findings suggest a potential relationship between domain formation and apoptotic activity. Liquid chromatography-mass spectrometry showed that the differences in apoptotic activity among the derivatives were unlikely attributed to variations in cellular uptake. Consequently, we propose that these ceramide derivatives accumulate and form distinct domains within the cellular membranes, inducing apoptosis. Intracellular ceramides synthesized in response to external stimuli may trigger apoptosis through the same mechanism.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118222"},"PeriodicalIF":3.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908304","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}

引用次数: 0

Novel sulfamide-hydroxamic acids containing piperazine/piperidine segment as potent urease inhibitors: Synthesis, biological evaluation, kinetics and molecular docking studies 新型含哌嗪/哌啶段脲酶抑制剂磺胺-羟肟酸：合成、生物学评价、动力学和分子对接研究

IF 3.3 3区医学

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-01 DOI: 10.1016/j.bmc.2025.118220

Yao Zeng , Wan-Qing Song , Liang-Chao Yuan , Meng-Jing Xiao , Zhu-Ping Xiao , Hai-Liang Zhu

{"title":"Novel sulfamide-hydroxamic acids containing piperazine/piperidine segment as potent urease inhibitors: Synthesis, biological evaluation, kinetics and molecular docking studies","authors":"Yao Zeng , Wan-Qing Song , Liang-Chao Yuan , Meng-Jing Xiao , Zhu-Ping Xiao , Hai-Liang Zhu","doi":"10.1016/j.bmc.2025.118220","DOIUrl":"10.1016/j.bmc.2025.118220","url":null,"abstract":"<div><div>Urease is known as a virulence factor of some pathogen resulting a variety of diseases such as peptic ulcers, gastric cancer, pyelonephritis, and kidney stones. In this paper, a novel series of sulfamide-hydroxamic acids containing piperazine/piperidine segment were designed, synthesized, and evaluated as urease inhibitors. All the synthesized compounds (<strong>d1-d16</strong> and <strong>d17-d33</strong>) having IC<sub>50</sub> values ranging from 0.29 to 20.3 µM were more potent than the clinically used inhibitor acetohydroxamic acid (AHA, IC<sub>50</sub> = 23.4 ± 1.6 μM), with the most active inhibitor (<strong>d4</strong>) being over 80 times that of AHA. These novel urease inhibitors were proved to reversibly inhibit urease with mixed mechanism, had almost no cytotoxicity to mammalian cells at a concentration of 250 μg/mL, and showed favorable water solubility with drug-likeness. These positive results give a guarantee for further bioassays to develop a new drug candidate.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118220"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911773","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}

引用次数: 0