Aggregate (Hoboken, N.J.)最新文献

{"title":"Solving the Amyloid Paradox: Unveiling the Complex Pathogenicity of Amyloid Fibrils","authors":"Maksim I. Sulatsky,&nbsp;Olesya V. Stepanenko,&nbsp;Olga V. Stepanenko,&nbsp;Anna I. Sulatskaya","doi":"10.1002/agt2.70078","DOIUrl":"https://doi.org/10.1002/agt2.70078","url":null,"abstract":"<p>More than a century ago, it was known that the accumulation of ordered protein aggregates, amyloid fibrils, accompanies several serious and still largely incurable pathologies, including Alzheimer's and Parkinson's diseases. The striking gap between decades of research identifying amyloids as one of the key drivers of neurodegeneration and the persistent lack of effective anti-amyloid therapies reveals a perplexing contradiction, which we define as the “amyloid paradox.” To address this paradox, here we summarize and analyze current perspectives on the unique properties and pathogenic mechanisms of amyloids, highlighting the variability and complexity of their biological consequences and uncovering the risks and limitations encountered in combating these aggregates. We conceptualize amyloid fibril pathogenicity as a complex cascade extending well beyond direct cytotoxicity, such as that arising from disruption of membranes and other cellular organelles. This review encompasses amyloids' disruptive effects on cellular processes and ability to trigger inflammatory responses, their resistance to degradation, capacity to regenerate after apparent destruction, tendency to propagate throughout the organism, propensity to cytotoxicity-increasing transformation, and ability to sequester and pathologically modify essential biomolecules. This integrated analysis reveals why single-target therapeutic approaches often fail and suggests that effective anti-amyloid strategies must address multiple aspects of amyloid pathogenicity simultaneously. The conceptual reframing of the threats of amyloid fibrils helps explain the origins of the amyloid paradox, enhances our understanding of these complex pathogenic agents, and provides a foundation for developing more effective and safe therapeutic strategies for neurodegenerative diseases. These strategies should address the complex and interconnected nature of amyloid pathogenicity rather than its targeting isolated aspects.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Linked Protein Crystals With an Intense Nonconventional Full-Color Photoluminescence Originating From Through-Space Intermolecular Interaction","authors":"Renbin Zhou,&nbsp;Xiaoli Lu,&nbsp;Xuefeng Zhou,&nbsp;Xuejiao Liu,&nbsp;Shanmin Wang,&nbsp;Tymish Y. Ohulchanskyy,&nbsp;Da-Chuan Yin,&nbsp;Junle Qu","doi":"10.1002/agt2.70070","DOIUrl":"https://doi.org/10.1002/agt2.70070","url":null,"abstract":"<p>The emergence of nonconventional luminescent materials (NLMs) has attracted significant attention due to their sustainable synthesis and tunable optical properties. Yet, establishing a clear structure–emission relationship remains a challenge. In this work, we report a previously unknown class of NLMs: cross-linked protein crystals that exhibit intense photoluminescence (PL) in the visible range (425–680 nm). We systematically investigated seven natural protein crystals (concanavalin, catalase, lysozyme, hemoglobin, α-chymotrypsin, pepsin, and β-lactoglobulin) cross-linked with glutaraldehyde and demonstrated that cross-linking induces broadband emission that is absent in natural crystals. Focusing on polymorphic lysozyme crystals (tetragonal, orthorhombic, and monoclinic), we found excitation-dependent fluorescence with lifetimes in the nanosecond range and quantum yields up to 20% (in the monoclinic phase under 450 nm excitation). Single- and two-photon spectroscopy, as well as pressure- and solvent-modulated PL studies, confirm that the emission is due to intermolecular through-space interactions (TSI) within the crystal lattice. Compression enhances TSI and redshifts the emission, whereas the solvent (DMSO)-induced swelling reduces TSI and causes a blue shift, establishing a direct structure–emission correlation. This work establishes protein crystals as programmable NLMs with tunable emission and provides a mechanistic framework for the design of nonconventional luminogens through protein crystal engineering.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aggregation-Induced Anti-Kasha Emission: Unraveling Multimodal Luminescence Mechanisms in a Single Molecule With Five Morphologies","authors":"Ling Yu,&nbsp;Yuzhang Liu,&nbsp;Dakai Zhou,&nbsp;Zhigang Ni,&nbsp;Shijun Li,&nbsp;Chuluo Yang","doi":"10.1002/agt2.70075","DOIUrl":"https://doi.org/10.1002/agt2.70075","url":null,"abstract":"<p>In recent years, the exploration of emission pathways from high-excited states in organic luminogens has received extensive attention owing to the anti-Kasha's rule emission with the potential of improving the exciton utilization. However, it is extremely difficult to predict the anti-Kasha effect and estimate the luminescent mechanism of high-energy excited states. We here present a rational design on the basis of the intermolecular noncovalent interactions to achieve the purpose of altering the molecular optoelectronic properties and regulating the distribution of high-energy excited state. The emitter, <i>p</i>-Py-SO₂-DMAC, with π–π dimer stacking is designed and synthesized, which not only exceptionally shows five aggregation morphologies and presents the infrequent aggregation-induced anti-Kasha's rule emission, room-temperature phosphorescence (RTP), and mechanoluminescence (ML) behaviors simultaneously, but also possesses the features of thermally activated delayed fluorescence (TADF) and aggregation-induced emission (AIE). The multiple luminescent mechanisms have been scientifically verified by experimental and theoretical investigations.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Stable Aggregation-Induced Emission-Functionalized Histatin1 Coated With Platelet Vesicles for Diabetic Wound Healing","authors":"Xiaoxuan Lei,&nbsp;Judun Zheng,&nbsp;Xu Chen,&nbsp;Liwen Liang,&nbsp;Zhuohong Li,&nbsp;Cancan Huang,&nbsp;Minghai Zhao,&nbsp;Gang Wu,&nbsp;Yuhui Liao,&nbsp;Bin Yang","doi":"10.1002/agt2.70073","DOIUrl":"https://doi.org/10.1002/agt2.70073","url":null,"abstract":"<p>The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress, increasing the risks of amputation and sepsis. Strategies based on bioactive substances, including recombinant growth factors and histatin proteins (Hsts), have been shown to promote skin-related cell migration, anti-inflammation, angiogenesis, and collagen deposition; however, their long-term stability remains a challenge. Herein, a platelet membrane-coated nanoparticle (PNP) system is proposed to achieve enhanced retention of aggregation-induced emissive (AIE) molecular-modified Hst1 (Hst1-AIE@PNPs) for more efficient repair of diabetic wounds. The Hst1-AIE@PNPs can not only protect Hst1 from degradation in the wound microenvironment but also permit visual monitoring of the controlled release of Hst1 through enhanced fluorescence in the enriched site. Combined with the antioxidant and anti-inflammatory properties of Hst1, Hst1-AIE@PNPs can effectively adsorb inflammation-related factors and further promote re-epithelialization and collagen deposition, thus achieving high-quality wound repair. The results highlight the potential of highly stable aggregation-induced-emission-functionalized Hst1 coated with platelet vesicles as a therapeutic platform to promote diabetic wound-related tissue restoration processes.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"π-Bridged Dimer Strategy of Aggregation-Induced Emission Molecules to Achieve Very Strong Absorption Ability","authors":"Liwei Dou,&nbsp;Huanlong Zheng,&nbsp;Haonan Xiong,&nbsp;Shengjie Fu,&nbsp;Chenguang Wang,&nbsp;Di Li","doi":"10.1002/agt2.70068","DOIUrl":"https://doi.org/10.1002/agt2.70068","url":null,"abstract":"<p>Aggregation-induced emission (AIE) molecules have attracted widespread attention due to their remarkable fluorescence properties in the aggregated state. However, the highly twisted structures of AIE molecules significantly disrupt the π-conjugations, thus resulting in weak absorption abilities (i.e., small molar absorption coefficients <i>ε</i>). To overcome this problem, herein we have proposed an efficient molecular design strategy: π-bridged dimer of AIE molecules. Accordingly, two series of AIE dimer molecules, TPE-BTO-Dimer 1‒6 and DTPE-BTO-Dimer 1‒6 with various π-bridged moieties, have been newly synthesized. In comparison to the corresponding AIE monomer molecules TPE-BTO and DTPE-BTO, the dimer molecules retain the AIE character while exhibit largely improved absorption abilities (the <i>ε</i> values are increased by 2.3‒3.7 times to 6.01‒9.54 × 10⁴ M⁻¹ cm⁻¹) as well as significantly redshifted absorption maxima. The theoretical calculations have revealed that the π-bridged dimer strategy dramatically increases the oscillator strength of electron transition from the ground state to an excited state and thus results in a large <i>ε</i>. In the transient absorption studies, the local excited state components of dimer molecules are obviously higher than those of monomer molecules, which further confirms the effectiveness of π-bridged dimer strategy. Moreover, one of the AIE dimer molecules DTPE-BTO-Dimer 6 with near-infrared (NIR) emission has been applied in NIR fluorescence imaging-guided photothermal therapy. The very strong absorption ability has enabled its nanoparticles to exhibit a high photothermal conversion efficiency of 73% under the 655 nm laser irradiation and thus display a desired photothermal therapy performance.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiresponsive Color-Tunable Phosphorescence With Matrix-Confined Clusters","authors":"Lihui Hou,&nbsp;Ting Wang,&nbsp;Siufung Yu,&nbsp;Xuhui Xu,&nbsp;Xue Yu","doi":"10.1002/agt2.70071","DOIUrl":"https://doi.org/10.1002/agt2.70071","url":null,"abstract":"<p>Ultralong organic phosphorescence (UOP) materials have garnered significant interest for applications in advanced optical recording and information encryption. However, it remains a formidable challenge achieving manipulated phosphorescence due to the limited color channels and poorly populated triplet energy levels. Herein, we report a novel multiresponsive organic phosphorescence material, in which the phosphorescence color can be dynamically tuned with stimuli such as radiation duration, concentration, excitation wavelength, time, and temperature. The material is based on the confined 7H-benzo[c]carbazole (BCz) molecules in the polymer matrix, which is achieved through the size-dependent cluster-triggered emission (CTE) mechanism. The BCz molecules form isolated molecules and different-sized clusters in the matrix, resulting in multiple luminescent centers with different energy levels and phosphorescence lifetimes. Through matrix confinement effects, the activation states of the monomers and multiple clusters could be precisely modulated, resulting in temperature-controlled tunable orange-to-green variations. Furthermore, the multiresponsive properties of the material have been used in both civil and military applications through sophisticated mathematical modeling. This work potentially proposes a guiding strategy for the development of multiresponsive UOP materials based on CTE molecules.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Active Learning Identifies Iron-Doped Carbon Dots With High Photothermal Conversion Efficiency for Antitumor Synergistic Therapy","authors":"Tianliang Li,&nbsp;Bin Cao,&nbsp;Yitong Wang,&nbsp;Lixing Lin,&nbsp;Lifei Chen,&nbsp;Tianhao Su,&nbsp;Haicheng Song,&nbsp;Yuze Ren,&nbsp;Longhan Zhang,&nbsp;Yingying Chen,&nbsp;Zhenzhen Li,&nbsp;Lingyan Feng,&nbsp;Tong-yi Zhang","doi":"10.1002/agt2.70060","DOIUrl":"https://doi.org/10.1002/agt2.70060","url":null,"abstract":"<p>Active learning (AL) is a powerful method for accelerating novel materials discovery but faces huge challenges for extracting physical meaning. Herein, we novelly apply an interpretable AL strategy to efficiently optimize the photothermal conversion efficiency (PCE) of carbon dots (CDs) in photothermal therapy (PTT). An equivalent value (SHapley Additive exPlanations equivalent value [SHAP-EV]) is proposed which explicitly quantifies the linear contributions of experimental variables to the PCE, derived from the joint SHAP values. The SHAP-EV, with an <i>R</i>² of 0.960 correlated to feature's joint SHAP, is integrated into the AL utility functions to enhance evaluation efficiency during optimization. Using this approach, we successfully synthesized iron-doped CDs (Fe-CDs) with PCE exceeding 78.7% after only 16 experimental trials over four iterations. This achievement significantly advances the previously low PCE values typically reported for CDs. Furthermore, Fe-CDs demonstrated multienzyme-like activities, which could respond to the tumor microenvironment (TME). In vitro and in vivo experiments demonstrate that Fe-CDs could enhance ferroptosis through synergistic PTT and chemodynamic therapy (CDT), thereby achieving remarkable antitumor efficacy. Our interpretable AL strategy offers new insights for accelerating bio-functional materials development in antitumor treatments.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A Modulates RAN Translation From CAG Repeat Expansion RNA","authors":"Yuxiang Sun,&nbsp;Zhouxian Li,&nbsp;Hui Dai,&nbsp;Yinsheng Wang","doi":"10.1002/agt2.70072","DOIUrl":"https://doi.org/10.1002/agt2.70072","url":null,"abstract":"<p>Nucleotide repeat expansions contribute to the development of a number of neurodegenerative diseases. Recent studies revealed that DNA sequences with CAG and other nucleotide repeat expansions can undergo bidirectional transcription, and the ensuing transcripts could be translated into proteins through repeat-associated non-AUG (RAN) translation; however, not much is known about the precise mechanisms underlying RAN translation. Here, we demonstrated that m⁶A, installed by METTL3 and removed by FTO, promotes RAN translation in all three reading frames from the expanded CAG repeat RNA derived from the human <i>ATXN3</i> gene, in which repeat expansion contributes to spinocerebellar ataxia type 3 (SCA3). Genetic depletion and pharmacological inhibition of METTL3 result in significantly diminished levels of RAN translation products from all three reading frames, which could be restored by ectopic expression of wildtype METTL3, but not its catalytically inactive mutant. Conversely, genetic ablation of FTO led to augmented RAN translation in all three reading frames. Moreover, one of the RAN translation products, poly(serine), exhibits gel-like aggregates in cells. Together, our study unveiled a crucial role of m⁶A in modulating RAN translation from expanded CAG repeat RNA transcribed from the human <i>ATXN3</i> gene, and documented new biophysical properties of the poly(serine) RAN translation product.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 7","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inside Front Cover: Circularly Polarized Luminescence Inversion in AIE-Active Crystal Enabled by Solvent-Induced Transition Dipole Moment Regulation","authors":"Xiaofei Niu,&nbsp;Xinwen Ou,&nbsp;Shizhe Ren,&nbsp;Ke Wang,&nbsp;Fengyan Song,&nbsp;Xiaobin Dong,&nbsp;Wu-Jie Guo,&nbsp;Hui-Qing Peng,&nbsp;Zujin Zhao,&nbsp;Jacky W. Y. Lam,&nbsp;Yong Sheng Zhao,&nbsp;Fei Li,&nbsp;Shu-Yan Yu,&nbsp;Ben Zhong Tang","doi":"10.1002/agt2.70065","DOIUrl":"https://doi.org/10.1002/agt2.70065","url":null,"abstract":"<p>This study elucidates a novel phenomenon in chiral AIEgens crystalline materials, demonstrating solvent-induced circularly polarized luminescence (CPL) sign inversion while maintaining identical helical configuration and molecular chirality in the crystalline state. The observed CPL reversal originates from non-bonding interactions between co-crystallized solvent molecules and AIEgens, which modulate the <i>θ</i>_μ,m (S₁→S₀) of electric and magnetic transition dipole moments within the unit cell. The findings establish a unique mechanism for chiroptical property manipulation through supramolecular engineering of non-covalent interactions in crystalline systems (e70003).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 5","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Back Cover: Integrating Aggregate Materials and Machine Learning Algorithms: Advancing Detection of Pathogen-Derived Extracellular Vesicles","authors":"Lihan Lai,&nbsp;Yun Su,&nbsp;Cong Hu,&nbsp;Zehong Peng,&nbsp;Wei Xue,&nbsp;Liang Dong,&nbsp;Tony Y. Hu","doi":"10.1002/agt2.70064","DOIUrl":"https://doi.org/10.1002/agt2.70064","url":null,"abstract":"<p>This review highlights cutting-edge strategies for enhancing the detection of pathogen-derived extracellular vesicles, including novel aggregate materials and machine learning approaches. Pathogen-derived vesicles are pivotal in host-pathogen interactions and possess significant diagnostic promise, as their unique cargo offers a rich repository of potential biomarkers. Enhancing vesicle detection may ultimately pave the way for transformative clinical applications (e70018).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"6 5","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}