bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface‐Functionalizable Plant‐Derived Extracellular Vesicles for Targeted Drug Delivery Carrier Using Grapefruit
Authors: Moon Kyunghwan , Hur Jihyeon , Kim Kwang Pyo , Lee Kangwon , Kang Ji Yoon 
Published: July 2023

AbstractRecently, membrane‐modified mammalian exosomes have been considered strong candidates for targeted drug delivery carriers because of their biocompatibility, biodistribution, and low immune response. However, the widespread utilization of exosomes still requires overcoming several challenging issues, including low stability, high production cost, and low mass productivity. Therefore, artificial extracellular vesicles (EVs) derived from cell membranes or liposomes containing various lipids have been suggested. However, only a few meet the demands of cost‐effective mass production and durability of EVs. Therefore, this study investigates the feasibility of replacing mammalian cell exosomes and liposomes with plant‐derived extracellular vesicles (pEVs) as targeted drug delivery carriers. They are characterized by nontoxicity, high stability, and high yield. Adding a functionalizable lipid moiety with a maleimide group at the membrane of grapefruit‐derived pEVs imparts targeting ability. The targeting function can be easily enhanced by attaching an aptamer using click chemistry. Indeed, treatment of brain cells with pEV‐aptamers (hCMEC/D3 and U87MG) confirms that aptamer functionalization of pEV enhanced selective cellular uptake. Functionalization of the pEV membrane using aptamer is expected to be effective in providing low‐cost and mass‐producible targeted drug delivery carriers with similar efficacy as mammalian exosomes or liposomes.
First‐Principle Study of Bandgap Engineering and Optical Properties of Monolayer WSe2 in Second Near‐Infrared Windows
Authors: Zhao Ruoli , Liu Ling , Pei Jiahui , Liu Changlong , Liu Tianyu , Zhang Xiao‐Dong 
Published: July 2023

AbstractFluorescence imaging in the second near‐infrared II (NIR‐II) window is opening up new possibilities in bioimaging due to its low scattering rate within the tissue. The integration of 2D materials with NIR‐II fluorescence will enable the development of multifunctional imaging probes. However, there are very few 2D materials that can fluoresce in the NIR‐II range. Monolayer WSe2 is a potential 2D material, but its photoluminescence (PL) around 790 nm is still far from the NIR‐II range due to its bandgap of 1.54 eV. In this study, it is investigated the electronic structures, dielectric functions, and PL spectra for Te, I, and Cr‐doped monolayer WSe2, as well as W and S vacant monolayer WSe2. Most of the defected monolayer WSe2 remain semiconductors, except for a few configurations exhibiting metallic properties after making vacancies. Among the monolayer WSe2 under investigation, the Cr‐doped WSe2 performs the best, exhibiting a strong PL peak in NIR‐II with a decreased bandgap around 1.0 eV. As increasing Cr concentration, the peak shifts further toward the red end of the spectrum due to an enhancement of p–d transition. The results provide a useful guideline for material synthesis applied in NIR‐II bioimaging and other biophysics.
Personalization of Complex Vaginal Inserts of Ethylene Vinyl Acetate via 3D‐Printing
Authors: Eder Simone , Kuchler Lisa , Katschnig Matthias , Brandl Bianca , Wolfgang Matthias , Koutsamanis Ioannis , Hentschel Lukas , Arbeiter Florian , Roblegg Eva , Spoerk Martin 
Published: July 2023

AbstractEthylene vinyl acetate (EVA) with a vinyl acetate (VA) content of 28 wt.% (EVA28) is frequently used in vaginal inserts and subcutaneous implants due to its biocompatibility and drug‐releasing properties. Traditionally being processed via hot melt extrusion, its processibility via filament‐based 3D‐printing was reported to be impossible. Consequently, no applicable customization concepts for vaginal inserts exist. For the first time, the fabrication of 3D‐printed vaginal inserts (urethra pessaries) of EVA28 is demonstrated by optimizing its viscosity, employing 3D‐printer adaptations, and carefully selecting printing parameters. The infill pattern of fully filled mono‐material pessaries (determining the number and orientation of weld lines) significantly affects the in vitro release of the model drug progesterone (P4), while other critical parameters (the pessary's mechanical properties and appearance) remain unaffected. Weld lines act as diffusion barriers for dissolved P4 molecules. Hence, a high number of weld lines to be crossed reduces the overall P4 diffusivity in EVA28, decreasing the P4 release rate. To further control the P4 release, innovative multi‐material pessary designs (additionally comprising EVA with a VA content of 9 wt.% that is also used in vaginal inserts) allow to tailor the in vitro drug release and the mechanics individually. Thereby, this work highly improves the mechanistic understanding on drug release modifications from 3D‐printed non‐biodegradable devices. The findings build the basis for the first application of customized vaginal inserts, as they are based on polymers used in corresponding marketed products for more than 20 years.
Turning Self‐Trapped Exciton Emission to Near‐Infrared Region in Thermochromism Zero‐Dimensional Hybrid Metal Halides
Authors: Bai Tianxin , Wang Xiaochen , He Yanmei , Wei Haiwen , Su Yan , Chen Junsheng 
Published: July 2023

AbstractLow dimensional lead‐free metal halides have become the spotlight of the research on developing multifunctional optoelectronic materials as their properties show a wide range of tunability. However, most reported low dimensional metal halides only function in the ultra‐violet to visible range due to their large bandgap. Moreover, the organic cation based low dimensional metal halides show limited thermal stability; on the other hand, their inorganic cation based counterparts suffer from limited solution processability. A hybrid cation approach is proposed, where a zero dimensional (0D) metal halide ((DFPD)2CsBiI6) is developed by using mixed organic–inorganic cations: 4, 4‐difluoropiperidine (DFPD) and cesium (Cs+). This ensures both thermal stability and solution processability. Furthermore, [BiI6]3− octahedra are serving as active light absorption units, which ensures the bandgap to be located at the visible region. Its photoluminescence (PL) is further shifted to the near infrared (NIR) region by doping (DFPD)2CsBiI6 with antimony (Sb3+). The developed materials show multifunctional properties: thermochromic behavior, light detection, and NIR light emitting. This study expands the scope of developing multifunctional 0D metal halides.
L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function
Authors: Wang Zekun , Yang Nana , Hou Yajun , Li Yuqing , Yin Chenyang , Yang Endong , Cao Huanhuan , Hu Gaofei , Xue Jing , Yang Jialei , Liao Ziyu , Wang Weiyun , Sun Dongdong , Fan Cundong , Zheng Lemin 
Published: July 2023

AbstractCardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L‐arginine‐loaded selenium‐coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)‐induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.
Small farms in North Carolina, United States: Analyzing farm and operator characteristics in the pursuit of economic resilience and sustainability
Authors: Quaicoe Obed , Asiseh Fafanyo , Baffoe‐Bonnie Anthony , Ng'ombe John N. 
Published: July 2023

AbstractEnsuring the sustainability of small farms relies on understanding farm economics, a crucial yet often overlooked aspect. In North Carolina, many small farms are confronted with financial challenges and the risk of collapse. This study examines the factors that influence farm profitability while considering the intersectionality of race and gender. The findings reveal significant disparities in farm and operator characteristics. Specifically, first‐generation and retiree farmers exhibit a lower likelihood of profitability. Conversely, factors positively associated with profitability include owning larger farm acreage, engaging in commercial agricultural production, utilizing paid family labor, practicing full‐time farming, and being a non‐White minority farmer. To foster the sustainability of small farms, it is imperative to implement policies that support full‐time farming and incentivize the use of paid family labor. These measures can contribute to bolstering profitability and safeguarding the economic viability of small farms.
Trans‐ethnic genomic informed risk assessment for Alzheimer's disease: An International Hundred K+ Cohorts Consortium study
Authors: Sleiman Patrick M. , Qu Hui‐Qi , Connolly John J. , Mentch Frank , Pereira Alexandre , Lotufo Paulo A. , Tollman Stephen , Choudhury Ananyo , Ramsay Michele , Kato Norihiro , Ozaki Kouichi , Mitsumori Risa , Jeon Jae‐Pil , Hong Chang Hyung , Son Sang Joon , Roh Hyun Woong , Lee Dong‐gi , Mukadam Naaheed , Foote Isabelle F. , Marshall Charles R. , Butterworth Adam , Prins Bram P. , Glessner Joseph T. , Hakonarson Hakon ,   Davos Alzheimer Collaborative and IHCC consortium
Published: July 2023

AbstractBACKGROUNDAs a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans‐ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD).METHODSThe GIRA model was created to include polygenic risk score calculated from the AD genome‐wide association study loci, the apolipoprotein E haplotypes, and non‐genetic covariates including age, sex, and the first three principal components of population substructure.RESULTSWe validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD.CONCLUSIONSAs the initial effort by the IHCC to leverage existing large‐scale datasets in a collaborative setting with DAC, we developed a trans‐ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.
Biomarker disclosure protocols in prodromal Alzheimer's disease clinical trials
Authors: Rahman‐Filipiak Annalise , Bolton Corey , Grill Joshua D. , Rostamzadeh Ayda , Chin Nathaniel , Heidebrink Judith , Getz Sarah , Fowler Nicole R. , Rosen Allyson , Lingler Jennifer , Wijsman Ellen , Clark Lindsay ,   for the Advisory Group on Risk Evidence Education in Dementia (AGREED)
Published: July 2023

AbstractINTRODUCTIONThe development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker “screening” criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown.METHODSWe reviewed the literature to identify prodromal AD trials published in the past 10 years. From these, we quantified the frequency of biomarker disclosure reporting and the depth of descriptions provided.RESULTSOf 30 published trials using positron emission tomography or cerebrospinal fluid‐based amyloid positivity as an eligibility criterion, only one mentioned disclosure, with no details on methods.DISCUSSIONPossible reasons for and implications of this information gap are discussed. Recommendations are provided for trialists considering biomarker screening as part of intervention trials focused on prodromal AD.HIGHLIGHTS
Few prodromal Alzheimer's disease (AD) trial papers discuss biomarker disclosure.
Disclosure has implications for participants, family members, and trial success.
Disclosure must be consistently integrated and reported in prodromal AD trials.
Best practice guidelines and training resources for disclosure are needed.
Membrane‐Vesicle‐Mediated Interbacterial Communication Activates Silent Secondary Metabolite Production
Authors: Yoshimura Aya , Saeki Rio , Nakada Ryusuke , Tomimoto Shota , Jomori Takahiro , Suganuma Keisuke , Wakimoto Toshiyuki 
Published: July 2023

AbstractMost bacterial biosynthetic gene clusters (BGCs) are “silent BGCs” that are expressed poorly or not at all under normal culture conditions. However, silent BGCs, even in part, may be conditionally expressed in response to external stimuli in the original bacterial habitats. The growing knowledge of bacterial membrane vesicles (MVs) suggests that they could be promising imitators of the exogenous stimulants, especially given their functions as signaling mediators in bacterial cell‐to‐cell communication. Therefore, we envisioned that MVs added to bacterial cultures could activate diverse silent BGCs. Herein, we employed Burkholderia multivorans MVs, which induced silent metabolites in a wide range of bacteria in Actinobacteria, Bacteroidetes and Proteobacteria phyla. A mechanistic analysis of MV‐induced metabolite production in Xenorhabdus innexi suggested that the B. multivorans MVs activate silent metabolite production by inhibiting quorum sensing in X. innexi. In turn, the X. innexi MVs carrying some MV‐induced peptides suppressed the growth of B. multivorans, highlighting the interspecies communication between B. multivorans and X. innexi through MV exchange.
The enhancement of antibacterial and anti‐biofouling properties of chitosan/silver nanoparticles‐grafted composite polyamide membrane
Authors: Duong Quan Xuan , Do Nguyen Hanh , Pham Hien Thanh , Ngo Thu Hong Anh 
Published: July 2023

AbstractThis study endeavors to augment the antibacterial and anti‐biofouling properties of thin‐film composite polyamide membranes by subjecting them to modification with antibacterial chitosan and silver nanoparticle materials through the UV‐induced graft polymerization technique. Various surface assessment methods were employed, and the efficiency of the membrane performance was demonstrated through the flux and the retention of the filtration process, which used calcium chloride as the foulant. Antibacterial, antifouling, and anti‐biofouling capabilities were assessed through several tests. The findings revealed that the chitosan/silver nanoparticles‐grafted membranes exhibited superior antibacterial and anti‐biofouling abilities with consistent flux and enhanced retention, underscoring the prospective implementation of this approach in filtration systems to curtail biofouling and bolster overall efficacy.
Data‐driven stability of stochastic mean‐field type games via noncooperative neural network adversarial training
Authors: Barreiro‐Gomez Julian , Choutri Salah E. 
Published: July 2023

AbstractWe propose an approach to neural network stochastic differential games of mean‐field type and its corresponding stochastic stability analysis by means of adversarial training (aka adversarial attacks). This is a class of data‐driven differential games where the distribution of the variables such as the system states and the decision‐makers' strategies (control inputs) is incorporated into the problem. This work casts the cooperative/noncooperative game terminology into the deep learning framework where we talk about cooperative and noncooperative neural network computations that involve learning capabilities and neural network architectures. We suggest a method to computationally validate the feasibility of the approximated solutions via neural networks and evaluate the stochastic stability of the associated closed‐loop system (state feedback Nash). Moreover, we enhance the stochastic stability by enlarging the training set with adversarial initial states to obtain a more robust neural network for a particular decision‐maker. Finally, a worked‐out example based on the linear‐quadratic mean‐field type game (LQ‐MTG) that illustrates our methodology is presented.
Emerging trends in materials and devices‐based electric stimulation therapy for tumors
Authors: Xie Shiwang , Huang Jing , Pereira Andreia Trindade , Xu Lingling , Luo Dan , Li Zhou 
Published: July 2023

AbstractElectrical stimulation (ES), as one of the physical therapy modalities for tumors, has attracted extensive attention of researchers due to its promising efficacy. With the continuous development of material science, nanotechnology, and micro/nano processing techniques, novel electroactive nanomaterials and delicately designed devices have emerged to realize innovative ES therapies, which provide more possibilities and approaches for tumor treatment. Meanwhile, exploring the molecular biological mechanisms underlying different ES modalities affecting tumor cells and their immune microenvironment is also an unresolved hotspot emerging from the current biomedical engineering research. Focusing on the above research interests, in this review, we systematically summarized the effects of different ES parameters on the subcellular structure of tumor cells and the tumor immune microenvironment (TIME) in conjunction with the involved signaling pathways. In addition, we also reviewed the latest progress in novel self‐powered devices and electroactive nanomaterials for tumor therapy. Finally, the prospects for the development of electrostimulation tumor therapy are also discussed, bringing inspiration for the development of new physical therapy strategies in the future.
Acetaminophen impairs ferroptosis in the hippocampus of septic mice by regulating glutathione peroxidase 4 and ferroptosis suppressor protein 1 pathways
Authors: Chu Jing , Li Hong , Yuan Zhihao , Zhou Wenyu , Yu Yang , Yu Yonghao 
Published: July 2023

AbstractBackgroundNeuronal ferroptosis is a major cause of cognitive impairment and mortality in patients with sepsis‐associated encephalopathy (SAE). A low dose of acetaminophen (APAP) in septic mice can prevent ferroptosis in the hippocampal tissue; however, the underlying mechanism is unknown. This study aimed to investigate the mechanism by which APAP reduces ferroptosis in the hippocampal tissues of septic mice.MethodsA mouse model of SAE was established, and the ferroptosis pathway inhibitors RSL3 and iFSP1+RSL3 were used in addition to APAP for the interventions, respectively. The 7‐day survival rate of the mice was recorded, and cognitive function was examined using the Morris water maze test. Hematoxylin and eosin staining was performed to observe hippocampal tissue damage. Hippocampal iron and malondialdehyde (MDA) were measured using chemical colorimetric methods. Immunofluorescence was used to detect the reactive oxygen species (ROS) content in hippocampal tissues.ResultsRSL3 reversed the efficacy of APAP on improving cognitive dysfunction in septic mice but did not obviously reverse the survival rate of mice enhanced by APAP. RSL3 aggravated APAP‐induced hippocampal tissue damage in mice attenuated by APAP. RSL3 inhibited glutathione peroxidase 4 (GPX4) expression and increased ferroptosis suppressor protein 1 (FSP1) and 4‐hydroxy‐2‐nonenal (4‐HNE) expression. RSL3 also reversed the effects of APAP in reducing iron, MDA, and ROS levels in the hippocampal tissues of septic mice. iFSP1+RSL3 further reversed the effect of APAP on ameliorating cognitive dysfunction in septic mice and successfully reversed the survival rate of mice enhanced by APAP. iFSP1+RSL3 aggravated APAP‐induced cerebral hippocampal damage. iFSP1+RSL3 inhibited both GPX4 and FSP1, further reversing the effect of APAP on the reduction in iron, 4‐HNE, ROS, and MDA levels in the cerebral hippocampus of mice with sepsis.ConclusionThese data suggest that APAP inhibits ferroptosis in the cerebral hippocampus of septic mice through the GPX4 and FSP1 pathways.
The effects of equine‐assisted activities on execution function in children aged 7–8 years: A randomized controlled trial
Authors: Cheng XiaoDong , Zhen KeXin , Fan Yongzhao , Tang Qian , Wu Hao 
Published: July 2023

AbstractBackground: This study examines the effects of equine‐assisted activity (EAA) training on executive functioning (EF) (inhibitory control, working memory, and cognitive flexibility) in children aged 7–8 years.Methods: Twenty‐Four healthy children aged 7–8 years with a 1:1 ratio of boys to girls were randomly divided into EAA group (EAAG) or control group (CG). The subjects in EAAG were trained for 12 weeks, and CG participated in normal daily activities. All subjects conducted the Flanker, 1‐Back, and More‐odd shifting tasks at rest and recorded the average reaction times (RTs) and accuracy data of each task.Results: After 12 weeks of EAA intervention, EAAG showed a highly significant increase (p < .01) in mean RTs and accuracy in the Flanker and More‐odd shifting tasks and a highly significant increase (p < .01) in accuracy only in 1‐Back.Conclusion: These findings suggest that 12‐week EAA training can be effective in improving EF and promoting cognitive performance in children aged 7–8 years.
Pluronic F127 “nanoarmor” for stabilization of Cowpea mosaic virus immunotherapy
Authors: Shin Matthew D. , Jung Eunkyeong , Moreno‐Gonzalez Miguel A. , Ortega‐Rivera Oscar A. , Steinmetz Nicole F. 
Published: July 2023

AbstractOur lab demonstrated that intratumoral Cowpea mosaic virus (CPMV) is a potent antitumor immunotherapy when used as in situ vaccine. As we pave the way for human clinical translation, formulation chemistry needs to be optimized for long‐term storage of the drug candidate. In this work, CPMV was nanoengineered with Pluronic F127 to realize liquid and gel formulations which mitigate structural changes and RNA release during long‐term storage. We evaluated the CPMV‐F127 formulations for their stability and biological activity through a combination of in vitro assays and efficacy in vivo using a B16F10 murine melanoma model. Results demonstrate that both F127 liquid and gel formulations preserve CPMV structure and function following extended periods of thermal incubation at 4°C, 25°C, and 37°C. Heat‐incubated CPMV without formulation resulted in structural changes and inferior in vivo efficacy. In stark contrast, in vivo efficacy was preserved when CPMV was formulated and protected with the F127 “nanoarmor.”