bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans- but Not Cis-Resveratrol Impairs Angiotensin-II–Mediated Vascular Inflammation through Inhibition of NF-κB Activation and Peroxisome Proliferator-Activated Receptor-γ Upregulation
Authors: Rius Cristina , Abu-Taha May , Hermenegildo Carlos , Piqueras Laura , Cerda-Nicolas Jose-Miguel , Issekutz Andrew C. , Estañ Luís , Cortijo Julio , Morcillo Esteban J. , Orallo Francisco , Sanz Maria-Jesus 
Published: August 2010

Abstract
Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II–induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1α. In an in vitro flow chamber system, t-RESV (1–10 μM) undermined the adhesion of human leukocytes under physiological flow to Ang-II–activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-κB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-γ in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-γ also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.
Alport Alloantibodies but Not Goodpasture Autoantibodies Induce Murine Glomerulonephritis: Protection by Quinary Crosslinks Locking Cryptic α3(IV) Collagen Autoepitopes In Vivo
Authors: Luo Wentian , Wang Xu-Ping , Kashtan Clifford E. , Borza Dorin-Bogdan 
Published: August 2010

Abstract
The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen.
The MAPK/ERK and PI(3)K Pathways Additively Coordinate the Transcription of Recombination-Activating Genes in B Lineage Cells
Authors: Novak Rostislav , Jacob Eyal , Haimovich Joseph , Avni Orly , Melamed Doron 
Published: August 2010

AbstractRag-1 and Rag-2 are essential for the construction of the BCR repertoire. Regulation of Rag gene expression is tightly linked with BCR expression and signaling during B cell development. Earlier studies have shown a major role of the PI(3)K/Akt pathway in regulating the transcription of Rag genes. In this study, by using the 38c13 murine B cell lymphoma we show that transcription of Rag genes is also regulated by the MEK/ERK pathways, and that both pathways additively coordinate in this regulation. The additive effect is observed for both ligand-dependent (upon BCR ligation) and ligand independent (tonic) signals. However, whereas the PI(3)K/Akt regulation of Rag transcription is mediated by Foxo1, we show in this study that the MEK/ERK pathway coordinates with the regulation of Rag by controlling the phosphorylation and turnover of E47 and its consequential binding to the Rag enhancer regions. Our results suggest that the PI(3)K and MEK/ERK pathways additively coordinate in the regulation of Rag transcription in an independent manner.
Upadacitinib in Active Non‐radiographic Axial Spondyloarthritis: 1‐Year Data From a Double‐Blind, Randomized, Placebo‐Controlled, Phase 3 Trial
Authors: Van den Bosch Filip , Deodhar Atul , Poddubnyy Denis , Maksymowych Walter P. , van der Heijde Désirée , Kim Tae‐Hwan , Kishimoto Mitsumasa , Baraliakos Xenofon , Li Yihan , D'Silva Kristin , Wung Peter , Song In‐Ho 
Published: May 2024

ObjectiveUpadacitinib improved the signs and symptoms of non‐radiographic axial spondyloarthritis (nr‐axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT‐AXIS 2 nr‐axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr‐axSpA in SELECT‐AXIS 2.MethodsPatients aged at least 18 years diagnosed with nr‐axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52‐week double‐blind period. Efficacy was assessed using non‐responder imputation incorporating multiple imputation (NRI‐MI) and as‐observed analyses for binary endpoints, and mixed‐effects model repeated measures for continuous endpoints.ResultsOf 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI‐MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI‐MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib.ConclusionTreatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit–risk profile of upadacitinib treatment for nr‐axSpA.
Intrabacterial Nitroreductase‐Activated Imaging and Persistently Illuminated Photodynamic Therapy for Intracellular Infection Theranostics
Authors: Ran Pan , Cao Wenxiong , Zheng Huan , Xie Shuang , Zhang Guiyuan , Liu Yuan , Li Xiaohong 
Published: May 2024

AbstractIntracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu2+ and persistence luminescent CaS:Eu2+ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics.
A Simple In Situ Marker Guiding Shape‐Controlled Synthesis of Iron Oxide Nanoparticles
Authors: Llacer‐Wintle Joaquin , Hertle Lukas , Ziegler Salomon , Pellicer Eva , Roca Alejandro G. , Nogués Josep , Puigmartí‐Luis Josep , Nelson Bradley J. , Chen Xiang‐Zhong , Pané Salvador 
Published: May 2024

AbstractThermal decomposition of iron oleate is a simple and widespread method for synthesizing monodispersed iron oxide nanoparticles (IONPs) with well‐defined morphology. However, the complexity of the underlying mechanism makes this method rather sensitive to variations in experimental conditions, and the lack of simple techniques to monitor the reaction progress in situ usually results in poor reproducibility and time‐consuming optimizations. Here, a simple, robust, and versatile in situ marker to monitor particle formation based on a sudden change in the temperature during reflux is reported. A linear relationship between the onset of particle formation and the concentration of surfactants is unveiled, corroborating a ‘chemically activated’ burst nucleation mechanism. Using this linear relationship as a guide, highly uniform spherical, cubic, and star‐shaped particles between 12 and 30 nm can be obtained. This temperature marker and the derived linear relationship not only deepen the understanding of the reaction process, but also provide a powerful tool for the straightforward optimization of IONPs.
Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro
Authors: Chen Maggie S. , Sun Rujie , Wang Richard , Zuo Yuyang , Zhou Kun , Kim Junyoung , Stevens Molly M. 
Published: May 2024

AbstractMany cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem‐cell derived cardiomyocytes (iPSC‐CMs) in a dose‐dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze‐like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low‐intensity magnetic field and on‐site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.
Sustained‐Release Hydrogen‐Powered Bilateral Microneedles Integrating CD‐MOFs for In Situ Treating Allergic Rhinitis
Authors: Ruan Hang , Long Meng , Li Jiaqi , Zhang Di , Feng Nianping , Zhang Yongtai 
Published: May 2024

AbstractGlucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin‐based metal–organic frameworks (CD‐MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH‐generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T‐bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH‐generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle‐mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse.
Investigation of the Single‐Particle Scale Structure–Activity Relationship Providing New Insights for the Development of High‐Performance Batteries
Authors: Wang Fei , Zhang Chong , Wu Fan , He Zhichao , Huang Yudong 
Published: May 2024

AbstractAs electric vehicles, portable electronic devices, and tools have increasingly high requirements for battery energy density and power density, constantly improving battery performance is a research focus. Accurate measurement of the structure–activity relationship of active materials is key to advancing the research of high‐performance batteries. However, conventional performance tests of active materials are based on the electrochemical measurement of porous composite electrodes containing active materials, polymer binders, and conductive carbon additives, which cannot establish an accurate structure–activity relationship with the physical characterization of microregions. In this review, in order to promote the accurate measurement and understanding of the structure–activity relationship of materials, the electrochemical measurement and physical characterization of energy storage materials at single‐particle scale are reviewed. The potential problems and possible improvement schemes of the single particle electrochemical measurement and physical characterization are proposed. Their potential applications in single particle electrochemical simulation and machine learning are prospected. This review aims to promote the further application of single particle electrochemical measurement and physical characterization in energy storage materials, hoping to achieve 3D unified evaluation of physical characterization, electrochemical measurement, and theoretical simulation at the single particle scale to provide new inspiration for the development of high‐performance batteries.
Entanglement Added to Cross‐Linked Chains Enables Tough Gelatin‐Based Hydrogel for Zn Metal Batteries
Authors: Kumankuma‐Sarpong James , Chang Caiyun , Hao Jing , Li Titi , Deng Xianming , Han Cuiping , Li Baohua 
Published: May 2024

AbstractCurrently, it is still challenging to develop a hydrogel electrolyte matrix that can successfully achieve a harmonious combination of mechanical strength, ionic conductivity, and interfacial adaptability. Herein, a multi‐networked hydrogel electrolyte with a high entanglement effect based on gelatin/oxidized dextran/methacrylic anhydride, denoted as ODGelMA is constructed. Attribute to the Schiff base network formulation of ─RC═N─, oxidized dextran integrated gelatin chains induce a dense hydrophilic conformation group. Furthermore, addition of methacrylic anhydride through a grafting process, the entangled hydrogel achieves impressive mechanical features (6.8 MPa tensile strength) and high ionic conductivity (3.68 mS cm−1 at 20 °C). The ODGelMA electrolyte regulates the zinc electrode by circumventing dendrite growth, and showcases an adaptable framework reservoir to accelerate the Zn2+ desolvation process. Benefiting from the entanglement effect, the Zn anode achieves an outstanding average Coulombic efficiency (CE) of 99.8% over 500 cycles and cycling stability of 900 h at 5 mA cm−2 and 2.5 mAh cm−2. The Zn||I2 full cell yields an ultra‐long cycling stability of 10 000 cycles with a capacity retention of 92.4% at 5 C. Furthermore, a 60 mAh single‐layer pouch cell maintains a stable work of 350 cycles.
General Fabrication of Robust Alloyed Metal Anodes for High‐Performance Metal Batteries
Authors: Yin Qingyang , Liu Qian , Liu Yatao , Qu Zhibin , Sun Fei , Wang Chongzhen , Yuan Xintong , Li Yuzhang , Shen Li , Zhang Chi , Lu Yunfeng 
Published: May 2024

AbstractRevitalizing metal anodes for rechargeable batteries confronts challenges such as dendrite formation, limited cyclicity, and suboptimal energy density. Despite various efforts, a practical fabrication method for dendrite‐free metal anodes remains unavailable. Herein, focusing on Li as exemplar, a general strategy is reported to enhance reversibility of the metal anodes by forming alloyed metals, which is achieved by induction heating of 3D substrate, lithiophilic metals, and Li within tens of seconds. It is demonstrated that preferred alloying interactions between substrates and lithiophilic metals created a lithiophilic metal‐rich region adjacent to the substrate, serving as ultrastable lithiophilic host to guide dendrite‐free deposition, particularly during prolonged high‐capacity cycling. Simultaneously, an alloying between lithiophilic metals and Li creates a Li‐rich region adjacent to electrolyte that reduces nucleation overpotential and constitutes favorable electrolyte‐Li interface. The resultant composite Li anodes paired with high areal loading LiNi0.8Co0.1Mn0.1O2 cathodes achieve superior cycling stability and remarkable energy density above 1200 Wh L−1 (excluding packaging). Furthermore, this approach shows broader applicability to other metal anodes plagued by dendrite‐related challenges, such as Na and Zn. Overall, this work paves the way for development of commercially viable metal‐based batteries that offer a combination of safety, high energy density, and durability.
Unlocking the Potential and Versatility of Quantum Dots: from Biomedical to Environmental Applications and Smart Micro/Nanorobots
Authors: Ussia Martina , Privitera Vittorio , Scalese Silvia 
Published: May 2024

AbstractQuantum dots (QDs) are recognized as the most promising functional nanotechnology, for which its discoverers are awarded the Nobel Prize in 2023. Their remarkable tunability of optoelectronic properties has attracted significant interest from both researchers and industries, placing QDs at the forefront of developing cutting‐edge technologies. This comprehensive review aims to explore the exciting results in terms of fundamental science, present and forthcoming applications. Beyond their contributions to biomedicine, energy, environmental science, quantum sensing, and quantum information processing, QDs have brought important results due to their integration into micro/nanorobotic systems, self‐propelled materials representing the state of the art research at the micro and nanoscale. These hybrid systems have demonstrated noteworthy outcomes, unlocking novel possibilities in biomedicine, quantum sensing, and environmental science, accurately reviewed in this article. In conclusion, this review addresses current challenges, offering insights to facilitate further research, stimulate new developments, and enhance the comprehension of the full potential of QDs.
Quercetin‐Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects
Authors: Zhu Huimin , Cai Chao , Yu Yeke , Zhou Yuning , Yang Shiyuan , Hu Yue , Zhu Yan , Zhou Jia , Zhao Jieyun , Ma Hailong , Chen Yujie , Xu Yuanjin 
Published: May 2024

AbstractPeriodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug‐controlled delivery system is constructed as a bone‐enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug‐carrying system made up of nanoscale bioglass microspheres and a light‐cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1‐dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.