bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cytoplasmic domain of FcγRIIA (CD32) participates in phagolysosome formation
Authors: Worth Randall G. , Mayo-Bond Laura , Kim Moo-Kyung , van de Winkel Jan G. J. , Todd Robert F. , Petty Howard R. , Schreiber Alan D. 
Published: July 2002

AbstractSignaling motifs located within the cytoplasmic domain of certain receptors contribute to lysosome fusion. Most studies have described lysosome fusion with respect to endocytic receptors. Phagolysosome fusion has not been extensively studied. To test the hypothesis that the tail of FcγRIIA participates in phagolysosomal fusion, a “reverse” genetic complementation system was used. It was previously shown that complement receptor type 3 (CR3) can rescue the phagocytic activity of a mutant FcγRIIA lacking its cytoplasmic domain (tail-minus form). This system has allowed us to study Fcγ receptor–dependent phagocytosis and phagolysosome fusion in the presence and absence of the cytoplasmic domain of FcγRIIA. Fluorescent dextran was used to label lysosomes. After target internalization, wild-type FcγRIIA–mediated phagolysosome formation was observed as indicated by colocalization of fluorescent dextran and the phagosome. In addition, when studying mutants of FcγRIIA containing a full-length cytoplasmic tail with the 2 ITAM tyrosines mutated to phenylalanine, (1) phagocytosis was abolished, (2) CR3 restored phagocytosis, and (3) lysosomal fusion was similar to that observed with the wild-type receptor. In contrast, in the presence of CR3 and the tail-minus form of FcγRIIA, internalized particles did not colocalize with dextran. Electron microscopy revealed that the lysosomal enzyme acid phosphatase colocalized with immunoglobulin G–coated targets internalized by wild-type FcγRIIA but not by tail-minus FcγRIIA and CR3. Thus, the tail of FcγRIIA contributes to phagolysosome fusion by a mechanism that does not require a functional ITAM sequence.
Efficient identification of HLA-A*2402–restricted cytomegalovirus-specific CD8+ T-cell epitopes by a computer algorithm and an enzyme-linked immunospot assay
Authors: Kuzushima Kiyotaka , Hayashi Naomi , Kimura Hiroshi , Tsurumi Tatsuya 
Published: July 2002

AbstractAntigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are useful tools for studying the CTL responses exclusively among those who own the major histocompatibility complex (MHC) class I molecules that present the peptides. For widening the application, an efficient strategy to determine such epitopes in the context of a given MHC is highly desirable. A rapid and efficient strategy is presented for the determination of CTL epitopes in the context of given MHC molecules of interest through multiple screenings consisting of a computer-assisted algorithm and MHC stabilization and enzyme-linked immunospot assays. A major cytomegalovirus (CMV)–specific CTL epitope, QYDPVAALF, in the amino acid sequence of its lower matrix 65 kd phosphoprotein (pp65) presented by HLA-A*2402 molecules was identified from 83 candidate peptides. The results indicate that the CMV-specific CTL response is highly focused to pp65 in the context of HLA-A*2402. Endogenous processing and presentation was confirmed using a peptide-specific CD8+ T-cell clone as the effectors and autologous fibroblast cells infected with recombinant vaccinia virus expressing pp65 gene or CMV as antigen-presenting cells. Flow cytometric analysis of intracellular interferon-γ production revealed 0.04% to 0.27% of CD8+ T cells in peripheral blood of HLA-A24+ and CMV-seropositive donors to be specific for the peptide. The tetrameric MHC-peptide complexes specifically bound to the reactive T-cell clone and 0.79% of CD8+ T cells in peripheral blood from a seropositive donor. The peptide could be a useful reagent to study CTL responses to CMV among populations positive for HLA-A*2402.
Adoptive transfer of simian immunodeficiency virus (SIV) naı̈ve autologous CD4+ cells to macaques chronically infected with SIV is sufficient to induce long-term nonprogressor status
Authors: Villinger Francois , Brice Gary T. , Mayne Ann E. , Bostik Pavel , Mori Kazuyasu , June Carl H. , Ansari Aftab A. 
Published: July 2002

AbstractAdoptive transfer of autologous preinfection-collected peripheral blood mononuclear cells (PBMCs) or activated CD4+ T cells was performed in simian immunodeficiency virus (SIVmac239)–infected monkeys following short-term antiviral therapy with PMPA (9-R-[2-phosphonylmethoxypropyl] adenine). Short-term chemotherapy alone led to a transient decrease in plasma and cellular proviral DNA loads and transient rescue of gag/pol and env cytotoxic T-lymphocyte precursors (pCTLs). However, cessation of therapy allowed for SIV infection to resume its clinical course. PMPA chemotherapy coupled with infusions of either autologous pre-SIV infection–collected PBMCs or activated CD4+ T cells led to extended control of plasma and cellular proviral DNA loads after infusion, in spite of the fact that the transfused cells were not primed against SIV. However, qualitatively different antiviral defenses were induced by infusion of unfractionated and unmanipulated PBMCs versus purified and activated CD4+ T cells: PBMC infusions significantly favored development of SIVenv-specific pCTLs, neutralizing antibodies, and secretion of soluble noncytotoxic suppressor factors of SIV replication. In contrast, activated CD4+ T cells predominantly promoted CTL responses to SIVgag/pol and SIVenv. In addition, infusion of influenza-primed activated CD4+ T cells markedly enhanced influenza-specific pCTL responses, whereas infusion of similarly influenza-primed unfractionated PBMCs enhanced such pCTL responses only modestly, suggesting that the predominant immune defect after SIV infection lies in the T helper cell compartment rather than the effector cell compartment. Thus, adoptive immunotherapy with autologous “SIV naı̈ve” CD4+ lymphocytes was sufficient to rescue cell-mediated immune responses and induce long-term anti-SIV control and immune responses in the absence of continued antiviral chemotherapy.
Acute Oxaliplatin-Induced Peripheral Nerve Hyperexcitability
Authors: Wilson Richard H. , Lehky Tanya , Thomas Rebecca R. , Quinn Mary G. , Floeter Mary Kay , Grem Jean L. 
Published: July 2002

PURPOSE: Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotoxicity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. PATIENTS AND METHODS: Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxaliplatin, detailed neurologic examination, needle electromyography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. RESULTS: All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitability in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. CONCLUSION: The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a major impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin.
Methylphenidate and Atomoxetine in Pregnancy and Possible Adverse Fetal Outcomes
Authors: di Giacomo Ester , Confalonieri Veronica , Tofani Fabio , Clerici Massimo 
Published: November 2024

ImportanceAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders, and it afflicts about 7% of young people. As a consequence, many young women might be pregnant while taking medication for ADHD, but data about safety have not yet been strictly examined.ObjectiveTo examine adverse effects in offspring of mothers receiving treatment with atomoxetine and methylphenidate during pregnancy.Data SourcesElectronic databases (PubMed, Embase, and PsycINFO) were searched for articles published through December 31, 2023, with the following search terms: (atomoxetine OR methylphenidate) AND (pregnancy).Study SelectionObservational studies (eg, cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) that reported offspring outcomes in pregnancy with atomoxetine and/or methylphenidate and in mothers with ADHD but unexposed to ADHD treatment during pregnancy or from the general population were included. Ten studies of 656 records satisfied criteria.Data Extraction and SynthesisTwo independent reviewers performed data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses were conducted based on reported odds ratios (ORs) and corresponding 95% CIs using a linear random effects model. Each study was inversely weighted by the reported variance of the estimators. Risk of publication bias and analysis of heterogeneity through univariate and multivariate metaregressions were also rated. Data were analyzed from January to March 2024.Main Outcomes and MeasuresStudy outcomes included miscarriages and congenital anomalies.ResultsTen studies involving 16 621 481 pregnant women, 30 830 of them affected by ADHD, were included. Congenital anomalies or miscarriages were not more frequent in offspring of mothers receiving treatment with methylphenidate or atomoxetine during pregnancy compared with unexposed offspring (OR, 1.14; 95% CI, 0.83-1.55; P = .41; I2 = 8% for congenital anomalies; OR, 1.01; 95% CI, 0.70-1.47; P = .96; I2 = 0% for miscarriages) or compared with the general population (OR, 1.19; 95% CI, 0.93-1.53; P = .16; I2 = 74% for congenital anomalies; OR, 1.05, 95% CI, 0.81-1.37; P = .70; I2 = 0% for miscarriage).Conclusions and RelevanceEvidence from this meta-analysis, which involves a substantial sample of pregnant women with and without ADHD, suggests the maintenance of methylphenidate or atomoxetine during pregnancy is safe, given that congenital anomalies and miscarriages did not appear to significantly increase. Further studies are recommended to support and confirm these findings.
Exploring the Intracellular Distribution of Se Compounds Delivered by Biodegradable Polyelectrolyte Capsules Using X‐Ray Fluorescence Imaging
Authors: Skiba Marvin , Reszegi Rebeka R. , Huang Yalan , Roy Sathi , Han Jili , Brückner Dennis , Sanchez‐Cano Carlos , Zhao Ying , Hassan Moustapha , Feliu Neus , Falkenberg Gerald , Parak Wolfgang J. 
Published: November 2024

AbstractSelenium (Se) compounds hold promise as potential therapeutics for cancer due to their diverse biological functions and redox‐regulating properties. In this study, the encapsulation of a hydrophobic selenium compound inside 5 µm sized biodegradable polyelectrolyte capsules consisting of poly‐L‐arginine and dextran is investigated. While the encapsulated form of the compound showed comparable cellular uptake and cytotoxicity as the free drug, e.g. no improved anti‐cancer efficacy is achieved, the investigation yielded crucial insights. Utilizing subcellular resolution synchrotron X‐ray fluorescence imaging (XFI), the intracellular location of the Se compound is successfully visualized by demonstrating the degradation of the capsules and the following redistribution of the compound, without exogenous labeling. By applying a quantitative fitting approach, the intracellular Se mass is determined to be 0.09 ± 0.01 pg after degradation of the carrier. This highlights the potential of XFI as a powerful tool for tracking intracellular dynamics of metal‐based drugs, which may facilitate drug development in the clinic.
Highly Parallel and High‐Throughput Nanoliter‐Scale Liquid, Cell, and Spheroid Manipulation on Droplet Microarray
Authors: Urrutia Gómez Joaquin E. , Zhou Meijun , Mandsberg Nikolaj K. , Serna Julian A. , von Padberg Julius , Liu Sida , Reischl Markus , Levkin Pavel A. , Popova Anna A. 
Published: November 2024

AbstractThe droplet microarray (DMA) platform is a powerful tool for high‐throughput biological and chemical applications, enabling miniaturization and parallelization of experimental processes. Capable of holding hundreds of nanoliter droplets, it facilitates the screening and analysis of samples, such as cells, bacteria, embryos, and spheroids. Handling thousands of small volumes in parallel presents significant challenges. In this study, we utilize the open format of the DMA for controlled, parallel high‐throughput liquid manipulations using the sandwich technique. We demonstrate high‐throughput medium replacement at nanoliter‐scale, maintaining high cell viability on DMA for up to 7 days; for HeLa‐CLL2 cells (adherent) and SU‐DHL4 cells (suspension), and up to 14 days for HEK293 spheroids. Additionally, we achieve highly parallel aliquot uptake from nanoliter droplets, enabling non‐destructive cell viability assessments. Furthermore, the presented method enables the parallel transfer of cell spheroids between different DMAs, allowing transfer and pooling of spheroids in seconds without damage. These advances significantly enhance the capabilities of the DMA platform, enabling long‐term cell culture in nanoliter droplets and parallel sampling for high‐throughput cell or spheroid manipulation. This broadens the scope of DMA's potential applications in fields such as cell‐based high‐throughput screening, formation of complex 3D cell models for drug screening, and microtissue engineering.
miR‐21‐Trigged Precise Photodynamic Therapy Through a “Locking‐Unlocking‐Boosting” ROS Production Strategy
Authors: Zhu Mengting , Liang Tao , Zhao Yupei , Li Zhen 
Published: November 2024

AbstractPhotodynamic therapy (PDT) stands out as a highly promising modality for tumor treatment, yet previous works have primarily centered around either boosting the production of reactive oxygen species (ROS) in tumor tissues or restricting it in normal tissues. The current challenge lies in the urgent need to achieve precise modulation of ROS production by simultaneously controlling both aspects. To achieve this goal, a precise PDT platform through a “locking‐unlocking‐boosting” ROS production strategy is presented, in which the generation of ROS is modulated by bidirectionally regulating the upconversion luminescence (UCL) of lanthanide‐doped nanoparticles (LnNPs), thus ROS production is “locked” in normal tissues but “boosted” in tumor tissues. In detail, by introducing an energy acceptor BHQ3, the UCL is initially quenched to prevent Chlorin e6 (Ce6) from generating ROS. However, under the tumor microenvironment with overexpressed miR‐21, LnNPs are sequestered from BHQ3 to “unlock” ROS generation and then assembled with QDs@B2, which functions as an antenna to sensitize LnNPs luminescence, to further “boost” ROS generation. With the assistance of spherical nucleic acids, this therapeutic agent effectively traverses the blood‐brain barrier (BBB), enabling efficient PDT for glioblastoma.
Composite Scaffold Materials of Nanocerium Oxide Doped with Allograft Bone: Dual Optimization Based on Anti‐Inflammatory Properties and Promotion of Osteogenic Mineralization
Authors: Li Yuqiao , Huang Yongkang , Yang Houzhi , Li Yuxin , Luo Gan , Ma Yuan , Cheng Haiyang , Long Yubin , Xia Weiwei , Liu Haiying , Fang Huayi , Du Yaping , Sun Tianwei , Wang Kaifeng , Zhai Xinyun 
Published: November 2024

AbstractSpinal fusion technique is widely used in the treatment of lumbar degeneration, cervical instability, disc injury, and spinal deformity. However, it is usually accompanied by a high incidence of fusion failure and pseudoarthrosis, placing higher demands on bone implants. Therefore, materials with good biocompatibility, osteoconductivity, and even induce bone ingrowth, which can be used to improve spinal fusion rate and bone regeneration, have become a hot research topic. Here, ultra‐small cerium oxide nanoparticles (CeO2 NPs) are prepared and loaded onto the surface of the homograft bone surface to prepare a composite scaffold AB@PLGA/CeO2. The composite scaffold shows the competitive ability to promote osteoblast differentiation in vitro. In vivo experiments show that AB@PLGA/CeO2 has a good bone enhancement effect. In particular, good biological effects of collagen fiber formation, osteogenic mineralization, and tissue repair are shown in intervertebral implant fusion. Further, transcriptome sequencing confirms that CeO2 NPs promote osteogenic differentiation and mineralization by regulating extracellular matrix (ECM) and collagen formation. Meanwhile, CeO2 NPs can regulate the function of the PI3K‐Akt signaling pathway to exert its ability to promote osteogenic differentiation and mineralization and affect p53 and cell cycle signaling pathway to regulate osteogenic differentiation and mineralization. Hence, the proposed scaffold is a promising strategy for intervertebral fusion in the clinic.
Boosting mRNA‐Engineered Monocytes via Prodrug‐Like Microspheres for Bone Microenvironment Multi‐Phase Remodeling
Authors: Wu Yuansheng , Zhu Yingjie , Chen Jie , Song Lili , Wang Chunping , Wu Yanglin , Chen Yanyang , Zheng Jiancheng , Zhai Yuankun , Zhou Xiang , Liu Youwen , Du Yawei , Cui Wenguo 
Published: November 2024

AbstractMonocytes, as progenitors of macrophages and osteoclasts, play critical roles in various stages of bone repair, necessitating phase‐specific regulatory mechanisms. Here, icariin (ICA) prodrug‐like microspheres (ICA@GM) are developed, as lipid nanoparticle (LNP) transfection boosters, to construct mRNA‐engineered monocytes for remodeling the bone microenvironment across multiple stages, including the acute inflammatory and repair phases. Initially, ICA@GM is prepared from ICA‐conjugated gelatin methacryloyl via a microfluidics system. Then, monocyte‐targeting IL‐4 mRNA‐LNPs are then prepared and integrated into injectable microspheres (mRNA‐ICA@GM) via electrostatic and hydrogen bond interactions. After bone‐defect injection, LNPs are controlled released from mRNA‐ICA@GM within 3 days, rapidly transfecting monocytes for monocyte IL‐4 mRNA‐engineering, which effectively suppressed acute inflammatory responses via polarization programming and paracrine signaling. Afterwards, ICA is sustainably released as well via cleavable boronate esters across multiple stages, cooperatively boosting the mRNA‐engineered monocytes to inhibit coenocytic fusion and osteoclastic function. Both in vitro and in vivo data indicated that mRNA‐ICA@GM can not only reverse the inflammatory environment but also suppress monocyte‐derived osteoclast formation to accelerate bone repair. In summary, mRNA‐engineered monocytes and ICA prodrug‐like microspheres are combined to achieve long‐lasting multi‐stage bone microenvironment regulation, offering a promising repair strategy.
Sustainable Biopolymers in Eco‐Friendly Triboelectric Energy Harvesting
Authors: Li Zekun , Yu Aifang , Zhai Junyi , Wang Zhong Lin 
Published: November 2024

AbstractBiopolymer‐based triboelectric nanogenerators (B‐TENGs) represent an innovative fusion of eco‐friendly, sustainable energy‐harvesting technology with renewable and environmentally benign biopolymer material. This integration not only introduces novel pathways for advancing green energy solutions but also offers a critical approach to addressing contemporary environmental challenges and fostering sustainable progress. Over the past few years, B‐TENGs have seen rapid and remarkable growth in the realm of biopolymers, device architecture, and their applications (e.g., implantable power source, electronic medicine, human anatomical and physiological movements monitoring sensors, etc.). In this review article, the promising developments in harnessing triboelectric biopolymers are encapsulated, enumerate their representative applications, evaluate the pros and cons of these biopolymers, highlight key challenges for future research, and offer strategic recommendations for innovating and realizing advanced B‐TENGs.
Controllable Synthesis of BixOyBrz/TiO2 Heterojunctions with Excellent Visible‐Light‐Driven Photocatalytic Activities for Phenol
Authors: Fang Guoli , Niu Zhuoyi , Zhang Gang , Yan Xianghui , Wei Jie , Israr Jahanzaib 
Published: November 2024

AbstractBixOyBrz/TiO2 composites have been synthesized by hydrothermal method, with TiO2 nanoparticles being employed as substrate. During the process of hydrothermal reaction, both temperature and pH have been utilized to effectively regulate the Bi/Br atomic ratio of BixOyBrz/TiO2 composites. In essence, the competitive reaction between OH− and Br− in the solution is the key factor to form BixOyBrz with different Bi/Br atomic ratios. Under visible light, the prepared Bi4O5Br2/TiO2 heterojunction demonstrates higher photocatalytic activity than other BixOyBrz/TiO2 composites for phenol and Rh B. The removal rate of phenol with Bi4O5Br2/TiO2 heterojunction is up to 92.1% after irradiation for 75 min. The excellent photocatalytic activities of Bi4O5Br2/TiO2 heterojunction are mainly attributed to its optimized microstructure and the matching band energy structure, whereby TiO2 nanoparticles with ≈10 nm diameter uniformly arranged on ≈10.2 nm thick Bi4O5Br2 nanosheets. Moreover, the heterojunction structure promotes the separation of photo‐generated electrons and holes in Bi4O5Br2/TiO2, while and h+ are the main active species during its photocatalytic processes.
Transparent, Sprayable Plastic Films for Luminescent Down‐Shifted‐Assisted Plant Growth
Authors: Müller Rosa , Okokhere‐Edeghoghon Bibian , Janowicz Norbert J. , Bond Andrew D. , Kociok‐Kohn Gabriele , Cox Lynne M. Roxbee , Garzon Diana , Waine Toby W. , Truckell Ian G. , Gage Ewan , Thompson Andrew J. , Busko Dmitry , Howard Ian A. , Saavedra Monica S. , Richards Bryce S. , Breiner Boris , Cameron Petra , Wright Dominic S. 
Published: November 2024

AbstractThe world's steadily growing population and global heating due to climate change are a threat to food security. To meet this challenge, novel technologies are needed to increase crop production in a sustainable way. In this work, the use of luminescent down‐shifting (LDS) materials based on molecular Eu3+‐containing polyoxotitanates for plant growth enhancement is investigated. Using a systematic design strategy to optimize down‐shifting properties, conversion of the ultraviolet spectral range to the photosynthetically active radiation (PAR) is achieved with quantum yields as high as 68%. The prototype Eu3+‐compound can be incorporated into water‐based acrylic varnish that can be spray‐coated onto existing greenhouses. Comparing coated with uncoated greenhouses, basil plants produce 9% more leaf dry weight per plant, and a highly significant 10% increase in individual leaf dry weight. The coating reduces the amount of transmitted PAR by 8% but has advantageous effects on diffuse radiation and in reducing the internal mean temperature. Although there is some uncertainty as to the contribution of down‐shifting, with the bulk of the increase probably being due to higher diffused light and the reduction in maximum daily temperatures, this study establishes a model for the design of LDS paints for real‐world agricultural applications.