Bioactive Materials最新文献

{"title":"Versatile effects of galectin-1 protein-containing lipid bilayer coating for cardiovascular applications","authors":"","doi":"10.1016/j.bioactmat.2024.08.026","DOIUrl":"10.1016/j.bioactmat.2024.08.026","url":null,"abstract":"<div><p>Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices. Inspired by the role of galectin-1 (Gal-1) in selective functions on multiple cells and immunomodulatory processes, we prepared a biologically target-specific surface coated with the lipid bilayer containing Gal-1 (Gal-1-SLB) and investigate the proof of the biological effects. First, lipoamido-dPEG-acid was deposited on a gold-coated substrate to form a self-assembled monolayer and then conjugated dioleoylphosphatidylethanolamine (DOPE) onto that to produce a lower leaflet of the supported lipid bilayer (SLB) before fusing membrane-derived vesicles extracted from B16-F10 cells. The Gal-1-SLB showed the expected anti-fouling activity by revealing the resistance to protein adsorption and bacterial adhesion. <em>In vitro</em> studies showed that the Gal-1-SLB can promote endothelial function and inhibit smooth muscle cell proliferation. Moreover, Gal-1- SLB presents potential function for endothelial cell migration and angiogenic activities. <em>In vitro</em> macrophage culture studies showed that the Gal-1-SLB attenuated the LPS-induced inflammation and the production of macrophage-secreted inflammatory cytokines. Finally, the implanted Gal-1-SLB reduced the infiltration of immune cells at the tissue-implant interface and increased markers for M2 polarization and blood vessel formation <em>in vivo</em>. This straightforward surface coating with Gal-1 can be a useful strategy for modulating the vascular and immune cells around a blood-contacting device.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003645/pdfft?md5=d351a0d06889bde18990ba6886a00733&pid=1-s2.0-S2452199X24003645-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic compliance penis enlargement patch","authors":"","doi":"10.1016/j.bioactmat.2024.08.039","DOIUrl":"10.1016/j.bioactmat.2024.08.039","url":null,"abstract":"<div><p>Men are particularly sensitive to penis size, especially those with a deformed or injured penis. This can lead to a strong desire for penis enlargement surgery. Given the ethical sensitivities of the penis, penile implants need to be developed with both efficacy and safety. In this study, a polyvinyl alcohol (PVA) patch for penile enlargement prepared via cyclic freeze‒thaw cycles and alkaline treatment. The PVA hydrogels treated with 5 M NaOH had the best mechanical properties and stability. A negative Poisson's ratio structure is incorporated into the design of the enlargement patch, which allows it to conform well to the deformation of the penis. In rabbit models, the enlarged patches can effectively enlarge the penis without degradation or fibrosis while maintaining long-term stability <em>in vivo</em>. This innovation not only provides a safe option for patients in need of penile enlargement but also promises to make a broader contribution to the field of dynamic tissue repair.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003761/pdfft?md5=ba25fd8e9c8ef344e32b628f8aad3186&pid=1-s2.0-S2452199X24003761-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An immunotherapeutic hydrogel booster inhibits tumor recurrence and promotes wound healing for postoperative management of melanoma","authors":"","doi":"10.1016/j.bioactmat.2024.08.028","DOIUrl":"10.1016/j.bioactmat.2024.08.028","url":null,"abstract":"<div><p>Low tumor immunogenicity, immunosuppressive tumor microenvironment, and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence. Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings. GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism, thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy, which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death. In addition, GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment, recruiting more tumor-infiltrating T lymphocytes. GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance. Benefiting from the amplified systemic antitumor immunity, GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors. Moreover, GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against <em>Staphylococcus aureus</em> infections, thereby promoting postsurgical wound healing. Hence, this immunotherapeutic hydrogel booster, as a facile and effective postoperative adjuvant, possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003669/pdfft?md5=c1fbe41a4d63eae0ff952807b2382b31&pid=1-s2.0-S2452199X24003669-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotection on ischemic brain injury by Mg2+/H2 released from endovascular Mg implant","authors":"","doi":"10.1016/j.bioactmat.2024.08.019","DOIUrl":"10.1016/j.bioactmat.2024.08.019","url":null,"abstract":"<div><p>Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg²⁺/H₂ from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. <em>In vitro</em> analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg²⁺/H₂ delivery system for treating distant cerebral ischemic diseases.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003578/pdfft?md5=4c641464092fecb6b07cea55b6cecbc8&pid=1-s2.0-S2452199X24003578-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the power of artificial intelligence for human living organoid research","authors":"","doi":"10.1016/j.bioactmat.2024.08.027","DOIUrl":"10.1016/j.bioactmat.2024.08.027","url":null,"abstract":"<div><p>As a powerful paradigm, artificial intelligence (AI) is rapidly impacting every aspect of our day-to-day life and scientific research through interdisciplinary transformations. Living human organoids (LOs) have a great potential for <em>in vitro</em> reshaping many aspects of <em>in vivo</em> true human organs, including organ development, disease occurrence, and drug responses. To date, AI has driven the revolutionary advances of human organoids in life science, precision medicine and pharmaceutical science in an unprecedented way. Herein, we provide a forward-looking review, the frontiers of LOs, covering the engineered construction strategies and multidisciplinary technologies for developing LOs, highlighting the cutting-edge achievements and the prospective applications of AI in LOs, particularly in biological study, disease occurrence, disease diagnosis and prediction and drug screening in preclinical assay. Moreover, we shed light on the new research trends harnessing the power of AI for LO research in the context of multidisciplinary technologies. The aim of this paper is to motivate researchers to explore organ function throughout the human life cycle, narrow the gap between <em>in vitro</em> microphysiological models and the real human body, accurately predict human-related responses to external stimuli (cues and drugs), accelerate the preclinical-to-clinical transformation, and ultimately enhance the health and well-being of patients.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003657/pdfft?md5=4450891ab994d7f4a02b7f921da590ac&pid=1-s2.0-S2452199X24003657-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer's disease therapy","authors":"","doi":"10.1016/j.bioactmat.2024.08.029","DOIUrl":"10.1016/j.bioactmat.2024.08.029","url":null,"abstract":"<div><p>Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H₂) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H₂ face significant challenges in controlling H₂ release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H₂ evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll <em>a</em> (Chl<em>a</em>) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H₂ in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003670/pdfft?md5=a2c7b563a5e33ccb12c3159d90349eda&pid=1-s2.0-S2452199X24003670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect","authors":"","doi":"10.1016/j.bioactmat.2024.08.018","DOIUrl":"10.1016/j.bioactmat.2024.08.018","url":null,"abstract":"<div><p>Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled <em>in situ</em> under fluid-irrigated arthroscopic conditions. Our <em>in vitro</em> and <em>in vivo</em> experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003566/pdfft?md5=a514fcf0e9ef81b50fb12a665f47b3bc&pid=1-s2.0-S2452199X24003566-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovering skin-nerve interaction by nanoscale metal-organic framework for diabetic ulcers healing","authors":"","doi":"10.1016/j.bioactmat.2024.08.024","DOIUrl":"10.1016/j.bioactmat.2024.08.024","url":null,"abstract":"<div><p>Skin-nerve interaction plays an important role in promoting wound healing. However, in diabetic ulcers (DUs), the diabetic periphery neuropathy and excessive levels of reactive oxygen species (ROS) block skin-nerve interaction and further impede the DUs healing. Herein, we developed a nanoscale metal-organic framework loaded with nerve growth factor (NGF/Ce-UiO-66, denoted NGF/CU) for the treatment of DUs. The Ce-UiO-66 (CU) was applied as an antioxidant to scavenge ROS and reduce the inflammatory response while the NGF aided in the recovery of cutaneous nerves to further promote DUs healing. Both <em>in vitro</em> and <em>in vivo</em> experiments revealed the effective ability of NGF/CU for DUs healing. Subsequent RNA sequencing analysis revealed the mechanism that NGF/CU can improve wound healing by inhibiting the NF-κB signaling pathway and recovering the neuroendocrine system of the skin. This strategy of nerve regulation will provide more ideas for the treatment of DUs and other organ injuries.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003621/pdfft?md5=99bd3ef191a303547351ad0c06d21a99&pid=1-s2.0-S2452199X24003621-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner","authors":"","doi":"10.1016/j.bioactmat.2024.08.021","DOIUrl":"10.1016/j.bioactmat.2024.08.021","url":null,"abstract":"<div><p>Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N⁶-methyladenosine (m⁶A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m⁶A methylation.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003591/pdfft?md5=7509b406e8a283fc73a0146847e889f1&pid=1-s2.0-S2452199X24003591-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation","authors":"","doi":"10.1016/j.bioactmat.2024.08.020","DOIUrl":"10.1016/j.bioactmat.2024.08.020","url":null,"abstract":"<div><p>Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe³⁺ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time (<span><math><mrow><mo>&gt;</mo></mrow></math></span> 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X2400358X/pdfft?md5=9783ffaeef6eae64b11d13b44ba70c4e&pid=1-s2.0-S2452199X2400358X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}