bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutral Nanocomplex Delivers Plasmid Encoding α‐Hemolysin for Uveal Melanoma Treatment
Authors: Wu Shanshan , He Liming , Yang Ling , Li Xun , Wang Jie , Ren Min , Gao Yunxia , Chen Yi , Wei Hong , Zhang Ming , Gou Maling 
Published: September 2024

AbstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults. Currently, the efficacy of existing eye‐preserving local treatments for primary UM is unsatisfactory, expressing a need to explore a new therapy for UM treatment. α‐Hemolysin (Hla), a pathogenic toxin fom Staphylococcus aureus, can induce cell death by disrupting the cell membrane and has potential antitumor effects. However, the broad toxicity of Hla limits its application in tumor therapy. In this study, the Hla‐based gene therapy strategy that uses plasmids to encode the Hla gene and applies tumor‐targeting nanoparticles to load the plasmids to form a nanocomplex is proposed. This gene formulation can overcome the obstructions of ocular barriers with its favorable neutral surface charge and nano size, allowing for precise targeting of tumor cells after local administration. The nanocomplex can effectively transfect tumor cells, and the expression of Hla can significantly inhibit tumor growth and directly exert a killing effect. Moreover, the nanocomplex can enhance the antitumor effect by recruiting CD4+ and CD8+ T lymphocytes and reducing angiogenesis after local administration. The study provides a novel gene therapy strategy for primary UM treatment and demonstrates a potential application for future gene therapy in intraocular tumors.
Targeting Dual Immune Checkpoints PD‐L1 and HLA‐G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer
Authors: Lin Yu‐Chuan , Chen Mei‐Chih , Huang Shi‐Wei , Chen Yeh , Ho Jennifer Hui‐Chun , Lin Fang‐Yu , Tan Xiao‐Tong , Chiang Hung‐Che , Huang Chiu‐Ching , Tu Chih‑Yen , Cho Der‐Yang , Chiu Shao‐Chih 
Published: September 2024

AbstractImmunotherapy targeting immune checkpoints (ICPs), such as programmed death‐ligand‐1 (PD‐L1), is used as a treatment option for advanced or metastatic non‐small cell lung cancer (NSCLC). However, overall response rate to anti‐PD‐L1 treatment is limited due to antigen heterogeneity and the immune‐suppressive tumor microenvironment. Human leukocyte antigen‐G (HLA‐G), an ICP as well as a neoexpressed tumor‐associated antigen, is previously demonstrated to be a beneficial target in combination with anti‐PD‐L1. In this study, a nanobody‐based trispecific T cell engager (Nb‐TriTE) is developed, capable of simultaneously binding to T cells, macrophages, and cancer cells while redirecting T cells toward tumor cells expressing PD‐L1‐ and/or HLA‐G. Nb‐TriTE shows broad spectrum anti‐tumor effects in vitro by augmenting cytotoxicity mediated by human peripheral blood mononuclear cells (PBMCs). In a humanized immunodeficient murine NSCLC model, Nb‐TriTE exhibits superior anti‐cancer potency compared to monoclonal antibodies and bispecific T cell engagers. Nb‐TriTE, at the dose with pharmacoactivity, does not induce additional enhancement of circulating cytokines secretion from PMBCs. Nb‐TriTE effectively prolongs the survival of mice without obvious adverse events. In conclusion, this study introduces an innovative therapeutic approach to address the challenges of immunotherapy and the tumor microenvironment in NSCLC through utilizing the dual ICP‐targeting Nb‐TriTE.
FGF12 Positively Regulates Keratinocyte Proliferation by Stabilizing MDM2 and Inhibiting p53 Activity in Psoriasis
Authors: Wang Nan , Xu Xiejun , Guan Fangqian , Lin Yifan , Ye Yizhou , Zhou Jie , Feng Jianjun , Li Sihang , Ye Junbo , Tang Zhouhao , Gao Wenjie , Sun Bohao , Shen Yingjie , Sun Li , Song Yonghuan , Jin Litai , Li Xiaokun , Cong Weitao , Zhu Zhongxin 
Published: September 2024

AbstractPsoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)‐induced psoriasis like‐dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ‐induced psoriasis model alleviates psoriasis‐like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β‐Trcp to MDM2. This interaction inhibits β‐Trcp‐induced‐K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.
m6A‐Dependent ITIH1 Regulated by TGF‐β Acts as a Target for Hepatocellular Carcinoma Progression
Authors: Liao Zhibin , Zhang Hongwei , Liu Furong , Wang Weijian , Liu Yachong , Su Chen , Zhu He , Chen Xiaoping , Zhang Bixiang , Zhang Zhanguo 
Published: September 2024

AbstractBoth the transforming growth factor beta (TGF‐β) signaling pathway and N6‐methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF‐β and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF‐β can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5β1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient‐derived organoid, patient‐derived xenografts), purified recombinant ITIH1 (r‐ITIH1) protein can be targeted for HCC. More importantly, r‐ITIH1 can play a synergistic role in targeting HCC with TGF‐β inhibitor. The downstream ITIH1 regulatory mechanism of TGF‐β and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.
Molecularly Imprinted Polymer Sensor Empowered by Bound States in the Continuum for Selective Trace‐Detection of TGF‐beta
Authors: Zito Gianluigi , Siciliano Giulia , Seifalinezhad Aida , Miranda Bruno , Lanzio Vittorino , Schwartzberg Adam , Gigli Giuseppe , Turco Antonio , Rendina Ivo , Mocella Vito , Primiceri Elisabetta , Romano Silvia 
Published: September 2024

AbstractThe integration of advanced materials and photonic nanostructures can lead to enhanced biodetection capabilities, crucial in clinical scenarios and point‐of‐care diagnostics, where simplified strategies are essential. Herein, a molecularly imprinted polymer (MIP) photonic nanostructure is demonstrated, which selectively binding to transforming growth factor‐beta (TGF‐β), in which the sensing transduction is enhanced by bound states in the continuum (BICs). The MIP operating as a synthetic antibody matrix and coupled with BIC resonance, enhances the optical response to TGF‐β at imprinted sites, leading to an augmented detection capability, thoroughly evaluated through spectral shift and optical lever analogue readout. The validation underscores the MIP‐BIC sensor capability to detect TGF‐β in spiked saliva, achieving a limit of detection of 10 fM and a resolution of 0.5 pM at physiological concentrations, with a precision of two orders of magnitude above discrimination threshold in patients. The MIP tailored selectivity is highlighted by an imprinting factor of 52, showcasing the sensor resistance to interference from other analytes. The MIP‐BIC sensor architecture streamlines the detection process eliminating the need for complex sandwich immunoassays and demonstrates the potential for high‐precision quantification. This positions the system as a robust tool for biomarker detection, especially in real‐world diagnostic scenarios.
Enzymolysis Modes Trigger Diversity in Inhibitor‐α‐Amylase Aggregating Behaviors and Activity Inhibition: A New Insight Into Enzyme Inhibition
Authors: Cao Junwei , Zhang Jifan , Cao Ruibo , Zhang Bin , Miao Ming , Liu Xuebo , Sun Lijun 
Published: September 2024

AbstractInhibitors of α‐amylase have been developed to regulate postprandial blood glucose fluctuation. The enzyme inhibition arises from direct or indirect inhibitor‐enzyme interactions, depending on inhibitor structures. However, an ignored factor, substrate, may also influence or even decide the enzyme inhibition. In this work, it is innovatively found that the difference in substrate enzymolysis modes, i.e., structural composition and concentration of α‐1,4‐glucosidic bonds, triggers the diversity in inhibitor‐enzyme aggregating behaviors and α‐amylase inhibition. For competitive inhibition, there exists an equilibrium between α‐amylase‐substrate catalytic affinity and inhibitor‐α‐amylase binding affinity; therefore, a higher enzymolysis affinity and concentration of α‐1,4‐glucosidic structures interferes the balance, unfavoring inhibitor‐enzyme aggregate formation and thus weakening α‐amylase inhibition. For uncompetitive inhibition, the presence of macromolecular starch is necessary instead of micromolecular GalG2CNP, which not only binds with active site but with an assistant flexible loop (involving Gly304‐Gly309) near the site. Hence, the refined enzyme structure due to the molecular flexibility more likely favors the inhibitor binding with the non‐active loop, forming an inhibitor‐enzyme‐starch ternary aggregate. Conclusively, this study provides a novel insight into the evaluation of α‐amylase inhibition regarding the participating role of substrate in inhibitor‐enzyme aggregating interactions, emphasizing the selection of appropriate substrates in the development and screening of α‐amylase inhibitors.
A Novel Asymmetric Diffusion Path for Superior Ion Dynamic in High‐Voltage Mg‐Based Hybrid Batteries
Authors: Huang Kaifeng , Qu Baihua , Shen Xing , Deng Rongrui , Li Rong , Huang Guangsheng , Tang Aitao , Li Qian , Wang Jingfeng , Pan Fusheng 
Published: September 2024

AbstractMagnesium‐based batteries have garnered significant attention due to their high energy density, excellent intrinsic safety, and low cost. However, the application process has been hindered by the high Mg2+ ions diffusion barrier in solid‐state structures and solid‐liquid interphase. To address this issue, a hybrid battery technology based on Mg anode and Fe‐based Prussian Blue Analogue cathode doped with functional transition metal ions and N═O bonds is proposed. Combined multiscale experimental characterizations with theoretical calculations, the subtle lattice distortion can create an asymmetric diffusion path for the active ions, which enables reversible extraction with significantly reduced diffusion barriers achieved by synergistic doping. The optimized cathode exhibits a working potential of 2.3 V and an initial discharge capacity of 152 mAh g−1 at 50 mA g−1. With the preferred electrolyte combined with equivalent concentration [Mg2(µ‐Cl)2(DME)4][AlCl4]2 and NaTFSI salt solution, the hybrid system demonstrates superior cycling performance over 200 cycles at a high current density of 200 mA g−1, maintaining ≈100% coulombic efficiency with superior ion dynamic. The findings are expected to be marked an important step in the further application of high‐voltage cathodes for Mg‐based hybrid batteries.
Spatial Confinement Engineered Gel Composite Evaporators for Efficient Solar Steam Generation
Authors: Yan Jun , Cui Tao , Su Qin , Wu Haidi , Xiao Wei , Ye Liping , Hou Suyang , Xue Huaiguo , Shi Yongqian , Tang Longcheng , Song Pingan , Gao Jiefeng 
Published: September 2024

AbstractRecently, solar‐driven interfacial evaporation (SDIE) has been developed quickly for low‐cost and sustainable seawater desalination, but addressing the conflict between a high evaporation rate and salt rejection during SDIE is still challenging. Here, a spatial confinement strategy is proposed to prepare the gel composite solar evaporator (SCE) by loading one thin hydrogel layer onto the skeleton of a carbon aerogel. The SCE retains the hierarchically porous structure of carbon aerogels with an optimized water supply induced by dual‐driven forces (capillary effects and osmotic pressure) and takes advantage of both aerogels and hydrogels, which can gain energy from air and reduce water enthalpy. The SCE has a high evaporation rate (up to 4.23 kg m−2 h−1 under one sun) and excellent salt rejection performance and can maintain structural integrity after long‐term evaporation even at high salinities. The SDIE behavior, including heat distribution, water transport, and salt ion distribution, is investigated by combining theoretical simulations and experimental results. This work provides new inspiration and a theoretical basis for the development of high‐performance interfacial evaporators.
Flexible Perovskite Solar Cells on Polycarbonate Film Substrates
Authors: Skafi Zeynab , Castriotta Luigi Angelo , Taheri Babak , Matteocci Fabio , Fahland Matthias , Jafarzadeh Farshad , Joseph Ebin , Chakraborty Abhisek , Singh Vaibhav , Mottaghitalab Vahid , Mivehi Leila , Brunetti Francesca , Sorbello Luca , Di Carlo Aldo , Brown Thomas M. 
Published: September 2024

AbstractThe market for polycarbonate (PC), a versatile material, is growing rapidly. Despite its widespread use in many applications, poor chemical resistance and roughness have hindered its adoption as a substrate in solar cell technologies. Here, the first‐ever perovskite solar cell (PSC) is demonstrated on PC films. A solution‐processed planarizing layer is developed using a commercial ambient‐curable refractory resin through blade coating which decreased film roughness from 1.46 µm to 23 nm, lowered water vapor transmission rates (WVTR) by a half, and significantly improved solvent resistance enabling deposition of precursor inks. The PSCs are fabricated on the planarized PC substrate, with a customized ITO electrode with an average visible transparency of 78%, sheet resistance of 25 Ω/sq, and a safe bending radius of 20 mm. The power conversion efficiency (PCE) reached 13.0%. The unencapsulated PSCs retained 80% of initial PCE after 1776 h upon ISOS‐D‐1 shelf‐life tests. These results open new pathways for integrating solar cells in many products made from PC materials, such as ID cards, smart cards, windows, skylights, buildings, and product packaging, as well as introducing a new solution for planarization and solvent barrier that can be used for other types of optoelectronic devices (LEDs, transistors, etc.) and substrates.
Influence of Post‐Synthesis Processing on the Structure, Transport, and Performance of the Solid Electrolyte Li5.5PS4.5Cl1.5 in All‐Solid‐State Batteries
Authors: Maus Oliver , Lange Martin A. , Frankenberg Finn , Stainer Florian , Faka Vasiliki , Schlautmann Eva , Rosenbach Carolin , Jodlbauer Anna , Schubert Johannes , Janek Jürgen , Li Cheng , Michalowski Peter , Wilkening H. Martin R. , Kwade Arno , Zeier Wolfgang G. 
Published: September 2024

AbstractWhile post‐synthesis processing steps are frequently applied in the preparation of cathode composites for solid‐state batteries to ensure homogeneous mixing and good contact with the cathode active material, little is known about the processes that occur during milling and how they influence structure and transport of solid electrolytes. Here, an extensive set of experimental methods and simulations are used to study the effects of post‐synthesis milling by a frequency and planetary ball mill on the highly conducting chloride‐rich argyrodite Li5.5PS4.5Cl1.5. Structural analyses show that processing can reduce the coherence length and increase the disorder. The reduced crystallite size correlates with a decrease in ionic conductivity in the post‐processed solid electrolytes. Simulating the ball milling processes by the discrete element method provides fundamental understanding and reveals the correlation of the loss in coherence with the specific energy input and the numbers of stressing events during the milling process. An observed decrease in particle size in ball milled samples leads to lower tortuosity in the cathode composites. As the loss in coherence and decrease in particle size have opposite effects on the performance, optimizing these processing conditions will play a significant role on the road to highly performing solid‐state batteries.
Storyteller in ADNI4: Application of an early Alzheimer's disease screening tool using brief, remote, and speech‐based testing
Authors: Skirrow Caroline , Meepegama Udeepa , Weston Jack , Miller Melanie J. , Nosheny Rachel L. , Albala Bruce , Weiner Michael W. , Fristed Emil ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: September 2024

AbstractINTRODUCTIONSpeech‐based testing shows promise for sensitive and scalable objective screening for Alzheimer's disease (AD), but research to date offers limited evidence of generalizability.METHODSData were taken from the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) studies (N = 101,N = 46 mild cognitive impairment [MCI]) and Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) remote digital (N = 426,N = 58 self‐reported MCI, mild AD or dementia) and in‐clinic (N = 57,N = 13 MCI) cohorts, in which participants provided audio‐recorded responses to automated remote story recall tasks in the Storyteller test battery. Text similarity, lexical, temporal, and acoustic speech feature sets were extracted. Models predicting early AD were developed in AMYPRED and tested out of sample in the demographically more diverse cohorts in ADNI4 (> 33% from historically underrepresented populations).RESULTSSpeech models generalized well to unseen data in ADNI4 remote and in‐clinic cohorts. The best‐performing models evaluated text‐based metrics (text similarity, lexical features: area under the curve 0.71–0.84 across cohorts).DISCUSSIONSpeech‐based predictions of early AD from Storyteller generalize across diverse samples.HighlightsThe Storyteller speech‐based test is an objective digital prescreener for Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4).Speech‐based models predictive of Alzheimer's disease (AD) were developed in the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) sample (N = 101).Models were tested out of sample in ADNI4 in‐clinic (N = 57) and remote (N = 426) cohorts.Models showed good generalization out of sample.Models evaluating text matching and lexical features were most predictive of early AD.
Missense and loss‐of‐function variants at GWAS loci in familial Alzheimer's disease
Authors: Gunasekaran Tamil Iniyan , Reyes‐Dumeyer Dolly , Faber Kelley M. , Goate Alison , Boeve Brad , Cruchaga Carlos , Pericak‐Vance Margaret , Haines Jonathan L. , Rosenberg Roger , Tsuang Debby , Mejia Diones Rivera , Medrano Martin , Lantigua Rafael A. , Sweet Robert A. , Bennett David A. , Wilson Robert S. , Alba Camille , Dalgard Clifton , Foroud Tatiana , Vardarajan Badri N. , Mayeux Richard 
Published: September 2024

AbstractBACKGROUNDFew rare variants have been identified in genetic loci from genome‐wide association studies (GWAS) of Alzheimer's disease (AD), limiting understanding of mechanisms, risk assessment, and genetic counseling.METHODSUsing genome sequencing data from 197 families in the National Institute on Aging Alzheimer's Disease Family Based Study and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study.RESULTSEighty‐six rare missense or loss‐of‐function (LoF) variants completely segregated in 17.5% of families, but in 91 (22.1%) families Apolipoprotein E (APOE)‐𝜀4 was the only variant segregating. However, in 60.3% of families, APOE 𝜀4, missense, and LoF variants were not found within the GWAS loci.DISCUSSIONAlthough APOE 𝜀4and several rare variants were found to segregate in both family datasets, many families had no variant accounting for their disease. This suggests that familial AD may be the result of unidentified rare variants.Highlights
Rare coding variants from GWAS loci segregate in familial Alzheimer's disease.
Missense or loss of function variants were found segregating in nearly 7% of families.
APOE‐𝜀4 was the only segregating variant in 29.7% in familial Alzheimer's disease.
In Hispanic and non‐Hispanic families, different variants were found in segregating genes.
No coding variants were found segregating in many Hispanic and non‐Hispanic families.
Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population‐based survey setting
Authors: Deza‐Lougovski Yacila I. , Weiss Luzia M. , Horton Hannah M. , Sun Aijing , Borbye‐Lorenzen Nis , Skogstrand Kristin , Holmgaard Solveig , Andersen‐Ranberg Karen , Lundmark Vania Panes , Börsch‐Supan Axel , Börsch‐Supan Martina , Rieckmann Anna 
Published: September 2024

AbstractINTRODUCTIONThe apolipoprotein E (APOE) ε4 allele carries risk for cognitive impairment, but whether the level of circulating apoE4 protein in carriers affects cognition is unclear, as is how health and lifestyle impact circulating apoE4 levels.METHODSWe assayed apoE4 protein levels in dried blood spots of 12,532 adults aged 50+. Regression analyses tested the likelihood of cognitive impairment between groups and within those with detected apoE4 protein. Predictors of circulating apoE4 were assessed.RESULTSWe detected protein binding that indicates the presence of an APOE ε4 allele in 28.4% of this group. This group was more likely to have cognitive impairment, and this risk increases with age. However, higher apoE4 levels were associated with less likelihood of cognitive impairment within this group. Antihypertensive medication predicted apoE4 protein levels.DISCUSSIONThe apoE4 isoform is associated with a deficient protein and worse cognition. This association is modulated by the level of circulating apoE4 protein in ε4 carriers.Highlights
An assay to quantify apoE4 levels from dried blood spot samples was applied.
The apoE4 protein was detected as specific binding at ≥30,000 pg/mL in 28.4% of samples.
Having the apoE4 protein was associated with worse cognitive performance.
Higher apoE4 protein levels in those who have it were associated with better cognition.
Cardiovascular factors influenced levels of apoE4 protein.