bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Generation of Rotavirus-Specific Human Monoclonal Antibodies from Small-Intestinal Mucosa
Authors: Di Niro Roberto , Mesin Luka , Raki Melinda , Zheng Nai-Ying , Lund-Johansen Fridtjof , Lundin Knut E. A. , Charpilienne Annie , Poncet Didier , Wilson Patrick C. , Sollid Ludvig M. 
Published: October 2010

Abstract
The gut mucosal surface is efficiently protected by Abs, and this site represents one of the richest compartments of Ab-secreting cells in the body. A simple and effective method to generate Ag-specific human monoclonal Abs (hmAbs) from such cells is lacking. In this paper, we describe a method to generate hmAbs from single Ag-specific IgA- or IgM-secreting cells of the intestinal mucosa. We found that CD138-positive plasma cells from the duodenum expressed surface IgA or IgM. Using eGFP-labeled virus-like particles, we harnessed the surface Ig expression to detect rotavirus-specific plasma cells at low frequency (0.03–0.35%) in 9 of 10 adult subjects. Single cells were isolated by FACS, and as they were viable, further testing of secreted Abs by ELISPOT and ELISA indicated a highly specific selection procedure. Ab genes from single cells of three donors were cloned, sequenced, and expressed as recombinant hmAbs. Of 26 cloned H chain Ab genes, 22 were IgA and 4 were IgM. The genes were highly mutated, and there was an overrepresentation of the VH4 family. Of 10 expressed hmAbs, 8 were rotavirus-reactive (6 with Kd &lt; 1 × 10−10). Importantly, our method allows generation of hmAbs from cells implicated in the protection of mucosal surfaces, and it can potentially be used in passive vaccination efforts and for discovery of epitopes directly relevant to human immunity.
Direct Inhibition of Human RANK+ Osteoclast Precursors Identifies a Homeostatic Function of IL-1β
Authors: Lee Bitnara , Kim Tae-Hwan , Jun Jae-Bum , Yoo Dae-Hyun , Woo Jin-Hyun , Choi Sung Jae , Lee Young Ho , Song Gwan Gyu , Sohn Jeongwon , Park-Min Kyung-Hyun , Ivashkiv Lionel B. , Ji Jong Dae 
Published: October 2010

Abstract
IL-1β is a key mediator of bone resorption in inflammatory settings, such as rheumatoid arthritis (RA). IL-1β promotes osteoclastogenesis by inducing RANKL expression on stromal cells and synergizing with RANKL to promote later stages of osteoclast differentiation. Because IL-1Rs share a cytosolic Toll–IL-1R domain and common intracellular signaling molecules with TLRs that can directly inhibit early steps of human osteoclast differentiation, we tested whether IL-1β also has suppressive properties on osteoclastogenesis in primary human peripheral blood monocytes and RA synovial macrophages. Early addition of IL-1β, prior to or together with RANKL, strongly inhibited human osteoclastogenesis as assessed by generation of TRAP+ multinucleated cells. IL-1β acted directly on human osteoclast precursors (OCPs) to strongly suppress expression of RANK, of the costimulatory triggering receptor expressed on myeloid cells 2 receptor, and of the B cell linker adaptor important for transmitting RANK-induced signals. Thus, IL-1β rendered early-stage human OCPs refractory to RANK stimulation. Similar inhibitory effects of IL-1β were observed using RA synovial macrophages. One mechanism of RANK inhibition was IL-1β–induced proteolytic shedding of the M-CSF receptor c-Fms that is required for RANK expression. These results identify a homeostatic function of IL-1β in suppressing early OCPs that contrasts with its well-established role in promoting later stages of osteoclast differentiation. Thus, the rate of IL-1–driven bone destruction in inflammatory diseases, such as RA, can be restrained by its direct inhibitory effects on early OCPs to limit the extent of inflammatory osteolysis.
IL-17A Is Proatherogenic in High-Fat Diet-Induced and Chlamydia pneumoniae Infection-Accelerated Atherosclerosis in Mice
Authors: Chen Shuang , Shimada Kenichi , Zhang Wenxuan , Huang Ganghua , Crother Timothy R. , Arditi Moshe 
Published: October 2010

Abstract
The role of IL-17 in atherogenesis remains controversial. We previously reported that the TLR/MyD88 signaling pathway plays an important role in high-fat diet as well as Chlamydophila pneumoniae infection-mediated acceleration of atherosclerosis in apolipoprotein E-deficient mice. In this study, we investigated the role of the IL-17A in high-fat diet (HFD)- and C. pneumoniae-induced acceleration of atherosclerosis. The aortic sinus plaque and aortic lesion size and lipid composition as well as macrophage accumulation in the lesions were significantly diminished in IL-17A−/− mice fed an HFD compared with wild-type (WT) C57BL/6 control mice. As expected, C. pneumoniae infection led to a significant increase in size and lipid content of the atherosclerotic lesions in WT mice. However, IL-17A−/− mice developed significantly less acceleration of lesion size following C. pneumoniae infection compared with WT control despite similar levels of blood cholesterol levels. Furthermore, C. pneumoniae infection in WT but not in IL-17A−/− mice was associated with significant increases in serum concentrations of IL-12p40, CCL2, IFN-γ, and numbers of macrophages in their plaques. Additionally, in vitro studies suggest that IL-17A activates vascular endothelial cells, which secrete cytokines that in turn enhance foam cell formation in macrophages. Taken together, our data suggest that IL-17A is proatherogenic and that it plays an important role in both diet-induced atherosclerotic lesion development, and C. pneumoniae infection-mediated acceleration of atherosclerotic lesions in the presence of HFD.
Enhanced Dendritic Cell Antigen Uptake via α2 Adrenoceptor-Mediated PI3K Activation Following Brief Exposure to Noradrenaline
Authors: Yanagawa Yoshiki , Matsumoto Machiko , Togashi Hiroko 
Published: October 2010

Abstract
Although noradrenaline (NA), a stress-associated neurotransmitter, seems to affect the immune system, the precise mechanisms underlying NA-mediated immunoregulation are not fully understood. We examined the effect of NA on Ag uptake (endocytosis) by dendritic cells (DCs) using murine bone marrow-derived DCs and fluorescence-labeled endocytic tracers (dextran and OVA). Ag uptake by DCs notably increased following a very brief treatment (3 min) with NA. NA-induced endocytosis was completely blocked by treatment with α2-adrenoceptor antagonist yohimbine. Neither α1-adrenoceptor antagonist prazosin nor β-adrenoceptor antagonist propranolol affected NA-induced endocytosis by DCs. A selective α2-adrenoceptor agonist, azepexole (B-HT 933), also significantly increased endocytosis by DCs. Thus, the α2-adrenoceptor seems to be responsible for NA-induced DC endocytosis. In parallel, NA markedly activated intracellular signaling pathways of PI3K and ERK1/2 in DCs. NA-mediated activation of these pathways was completely inhibited by yohimbine treatment. Blocking PI3K activation significantly reduced NA-induced endocytosis by DCs. Based on these results, NA rapidly enhances Ag capture by DCs via α2 adrenoceptor-mediated PI3K activation, which may be associated with immune enhancement following acute stress.
Cutting Edge: The Transcription Factor Eomesodermin Enables CD8+ T Cells To Compete for the Memory Cell Niche
Authors: Banerjee Arnob , Gordon Scott M. , Intlekofer Andrew M. , Paley Michael A. , Mooney Erin C. , Lindsten Tulia , Wherry E. John , Reiner Steven L. 
Published: October 2010

Abstract
CD8+ T cells responding to intracellular infection give rise to cellular progeny that become terminally differentiated effector cells and self-renewing memory cells. T-bet and eomesodermin (Eomes) are key transcription factors of cytotoxic lymphocyte lineages. We show in this study that CD8+ T cells lacking Eomes compete poorly in contributing to the pool of Ag-specific central memory cells. Eomes-deficient CD8+ T cells undergo primary clonal expansion but are defective in long-term survival, populating the bone marrow niche and re-expanding postrechallenge. The phenotype of Eomes-deficient CD8+ T cells supports the hypothesis that T-bet and Eomes can act redundantly to induce effector functions, but can also act to reciprocally promote terminal differentiation versus self-renewal of Ag-specific memory cells.
Host Genes Associated with HIV-1 Replication in Lymphatic Tissue
Authors: Smith Anthony J. , Li Qingsheng , Wietgrefe Stephen W. , Schacker Timothy W. , Reilly Cavan S. , Haase Ashley T. 
Published: October 2010

Abstract
Much effort has been spent recently in identifying host factors required for HIV-1 to effectively replicate in cultured human cells. However, much less is known about the genetic factors in vivo that impact viral replication in lymphatic tissue, the primary anatomical site of virus–host interactions where the bulk of viral replication and pathogenesis occurs. To identify genetic determinants in lymphatic tissue that critically affect HIV-1 replication, we used microarrays to transcriptionally profile and identify host genes expressed in inguinal lymph nodes that were associated determinants of viral load. Strikingly, ∼95% of the transcripts (558) in this data set (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset 1) inhibit cellular activation/proliferation (e.g., TCFL5, SOCS5 and SCOS7, KLF10), 2) promote heterochromatin formation (e.g., HIC2, CREBZF, ZNF148/ZBP-89), 3) increase collagen synthesis (e.g., PLOD2, POSTN, CRTAP), and 4) reduce cellular transcription and translation. Potential anti–HIV-1 restriction factors were also identified (e.g., NR3C1, HNRNPU, PACT). Only ∼5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all of these genes function in innate and adaptive immunity, particularly highlighting heightened gene expression in the IFN system. We conclude that this conventional host response cannot contain HIV-1 replication and, in fact, could well contribute to increased replication through immune activation. More importantly, genes that have a negative association with virus replication point to target cell availability and potentially new viral restriction factors as principal determinants of viral load.
Zinc–Silver Nitroprusside Nanocomposites: Synthesis, Characterization, and Antibacterial Properties with Cytocompatibility
Authors: Lu Yuting , Sathiyaseelan Anbazhagan , Zhang Xin , Wang Myeong‐Hyeon 
Published: February 2025

The emergence of bacterial infections poses an enormous health, economic, and global burden on organisms. However, silver‐based materials with strong antibacterial activity are difficult to apply due to the high toxicity. Therefore, zinc–silver nitroprusside nanocomposites (Zn–AgNP NCs) are prepared using sodium nitroprusside as a medium and characterized to achieve enhancement of their antibacterial properties and reduction of their cytotoxicity. Herein, the Zn–AgNP NCs show a cubic shape with an average size of 161.23 ± 3.77 nm and exhibit a negative zeta potential (–25 ± 0.23 mV). The Zn–AgNP NCs exhibit crystalline properties similar to those of silver nitroprusside nanoparticles (AgNP NPs) and zinc nitroprusside nanoparticles (ZnNP NPs). Furthermore, Zn–AgNP NCs demonstrate enhanced antibacterial and anti‐biofilm activities against multiple pathogens, including Bacillus cereus (MIC50 = 8.8 μg mL−1), and induce high levels of nucleic acid and protein leakage in bacteria. In addition, Zn–AgNP NCs demonstrate low cytotoxicity (below 15.6 μg mL−1) and high biocompatibility (up to 250 μg mL−1). Overall, Zn–AgNP NCs exhibit excellent antibacterial capabilities and superior biocompatibility compared to AgNP NPs. This study suggests that Zn–AgNP NCs have the potential to be utilized as a safe and effective antibacterial agent.
In Situ Self‐Assembly of Artificial Topological Nanostructures Enhances In Vivo Efficacy of PCSK9 Inhibitory Peptides
Authors: Li Qin , Mu Zhaode , Dong Yuhan , Ouyang Zubin , Zuo Jianli , Wu Yijie , Yang Yuxuan , Sun Si , Liang Hongwen , Bai Lijuan 
Published: February 2025

AbstractOptimizing the stability and affinity of peptides in vivo is critical for their development as alternatives to approved monoclonal antibodies. In recent years, efforts in academia and industry have focused on modifying Pep2‐8, a classical antagonistic peptide targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), to enhance its specificity and affinity. However, developing effective PCSK9 inhibitory peptides remains challenging, especially given the limited examples of their successful in vivo applications. Here, we designed transformable inhibitory peptide (TIP) against PCSK9 based on the modular structure of Pep2‐8. Upon encountering PCSK9, TIP undergoes in situ self‐assembly at the epidermal growth factor‐like domain A (EGF‐A) binding domain of PCSK9 to form artificial topological nanostructures (ATNs). The ATNs not only enhance peptide stability and prolong in vivo retention time but also strengthen PCSK9 binding through multivalent synergistic effects. We demonstrate that compared to Pep2‐8, TIP forms ATNs which increasing its binding affinity for PCSK9 by approximately 18.7‐fold in vitro. In high‐fat diet mouse models, TIP significantly increase hepatic LDLR levels (2.0‐fold) and reduced LDL‐C and TC levels. We envision that the in situ formation of ATNs by peptides enhances in vivo stability and affinity, which offering an approach for development as antibody alternatives in clinical.
Preparation and Properties of High Oxygen and Ultraviolet Barrier Biaxially Oriented Polyamide 6/Poly(M‐Xylene Adipamide)/Layered Cerium Oxide Film
Authors: Guo Jiushi , Lin Fenglong , Wang Xinkun , Du Jiahui , Yun Xueyan , Song Lijun , Dong Tungalag 
Published: February 2025

ABSTRACTPolyamide 6 (PA6) films exhibit low oxygen permeability, good puncture resistance, and high tensile strength, but require enhanced gas and UV barrier properties to better protect sensitive packaged contents from environmental factors. This study investigates the morphology, crystallization, mechanical and barrier properties of biaxial oriented of PA6/MXD6/L‐CeO2 films through the introduction of poly(m‐xylene adipamide) (MXD6) and layered cerium oxide (L‐CeO2). The results demonstrate that blending with MXD6 reduces the oxygen permeability. The addition of L‐CeO2 further improves both oxygen barrier and UV barrier of films. The biaxially oriented PA6/MXD6/L‐CeO2 film with 30% MXD6 and 1.5% L‐CeO2 has 22.0% less oxygen permeation and 69.9% less UV transmission (200–400 nm) than the film only with 30% MXD6. This study contributes to the development of PA6 films with enhanced barrier properties and evaluates the impact of layered cerium oxide filling on film performance.
Unlocking Resources for Source Water Protection in the Face of Climate Change
Authors: White David , Norton Kevin 
Published: February 2025

Key TakeawaysThe growing threats from extreme weather and climate‐related disasters require collaboration to protect regional water supplies.Building on the gains included in the 2018 Farm Bill, US water utilities now have greater opportunities to protect source waters and deliver both climate‐ and water‐related benefits.The recent Inflation Reduction Act created historic funding for and many points of access to landscape‐changing conservation practices.Supported by AWWA, water utilities have a range of tools and resources for working locally to expand conservation efforts and prioritize their implementation.
Circular Economy Outcomes in Banks: The Role of Environmental Strategy, Women, and the Sustainability Committee
Authors: Allodi Evita , Soana Maria Gaia 
Published: February 2025

ABSTRACTThe study investigates how environmental strategies, board gender diversity, and CSR committees affect the circular economy performance in the banking sector. For the first time, we focus on three specific reduction goals: GHG emission reduction, e‐waste reduction, and offering products to reduce the negative environmental impact. Using a sample of 671 listed worldwide banks from 63 countries in 2010–2021, we demonstrate that green strategies and CSR committees positively affect all three circular economy targets. However, board gender diversity positively impacts bank emission reduction and green products offered but does not influence e‐waste reduction. Furthermore, the presence of the CSR committee significantly improves the effectiveness of environmental strategies adopted by banks in achieving their circular economy performance. The 2015 Paris Agreement on climate change proves to be effective in enhancing bank circular economy reduction outcomes.
First‐In‐Human Dose Finding Study of Venadaparib (IDX‐1197), a Potent and Selective PARP Inhibitor, in Patients With Advanced Solid Tumors
Authors: Kim Sung‐Bae , Bae Kyun‐Seop , Lee Jae Lyun , Lee Won Sik , Ock Chan‐Young , Lee Myong‐Jae , Bang Jeongsook , Hong Min Ju , Roh Eun‐Jihn , Ha Kyoung Soo , Lim Jong‐Ha , Kim Yong‐Man 
Published: February 2025

ABSTRACTBackgroundVenadaparib, a novel poly (ADP‐ribose) polymerase (PARP) inhibitor, has demonstrated high PARP‐1/2 selectivity over other PARP family members and exhibited strong PARP‐trapping activity, effectively inhibiting tumor growth in homologous recombination deficient (HRD) cancer in vitro and in vivo.MethodsThis phase 1, dose‐finding study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib as monotherapy in patients with advanced solid tumors that progressed after standard‐of‐care therapy. The study employed a conventional 3+3 design, with doses ranging from 2 mg/d to 240 mg/d.ResultsAmong the 32 enrolled patients, the most common tumor types were breast (16 patients) and ovarian (12 patients) cancers. No dose‐limiting toxicities (DLTs) were observed up to 240 mg/d. The most frequent grade 3 or 4 adverse events were anemia (50%), neutropenia (22%) and thrombocytopenia (6%). Tumor shrinkage by Response Evaluation Criteria in Solid Tumours (RECIST) was observed at doses ≥ 40 mg/d, regardless of BRCA mutation status.Two partial responses out of four ovarian cancer patients receiving venadaparib ≥ 40 mg/d were reported. Clinical benefit, defined as stable disease or partial response, was observed at the lowest tested dose. Venadaparib exhibited ≥ 90% PAR inhibitory effect in pharmacodynamic analysis from 10 mg/d based on tumor samples. The recommended phase 2 dose (RP2D) was defined as 160 mg once daily.ConclusionsFurther studies are warranted to explore efficacy and safety of venadaparib in other tumor types and in combination with various agents, as well as to explore relevant biomarkers. (ClinicalTrials.gov ID: NCT03317743).
Development of A Caregiver‐Reported Scale for Pediatric Cancer Financial Toxicity (CRS‐PCFT)
Authors: Li Pengfei , Zhang Nan , Xu Xinyue , Liu Yan , Lu Zhengyang , Gao Qian , Lin Shihong , Guan Weimin , Yan Wenxuan , Liu Boyu , Lu Youhua , Yu Jinming 
Published: February 2025

ABSTRACTBackgroundFinancial toxicity is common among families of pediatric patients with cancer. However, the availability of survey and/or screening instruments specific to pediatric family financial toxicity is limited.MethodsA two‐round cross‐sectional survey was conducted in Shandong Province, China. We combined classical test theory (CTT) and item response theory (IRT) to validate items of the caregiver‐reported scale for pediatric cancer financial toxicity (CRS‐PCFT) after Delphi. The scale structure, reliability, and validity were determined and validated by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The threshold was discussed based on the correlations between CRS‐PCFT and socio‐factors.FindingsA 16‐item initial scale was determined after Delphi. The data from 206 pilot survey samples was used to select and validate items, and a 10‐item CRS‐PCFT was developed. The scale showed satisfactory reliability and validity based on data from 398 formal survey samples. When the CRS‐PCFT scores were into high and low toxicity groups by the median, they were significantly correlated with education (r = −0.284, p < 0.0001), household income (r = −0.253, p < 0.0001), work status (r = −0.173, p = 0.001), and cancer stages (r = 0.147, p = 0.003).InterpretationCRS‐PCFT demonstrates robust reliability and validity and makes it more accurate to obtain the pediatric cancer financial toxicity conditions. Additional research should be done to validate CRS‐PCFT.
Fragment‐Based Approach for Hierarchical Nanotube Assembly of Small Molecules in Aqueous Phase
Authors: Zia Ayisha , Yi Meihui , Liu Zhiyu , Wang Fengbin , Xu Bing 
Published: February 2025

AbstractA fragment‐based approach has proven successful in drug design and protein assemblies, yet its potential for constructing biomaterials from simple organic building blocks remains underexplored, particularly for self‐assembly in aqueous phases, where water disrupts intermolecular hydrogen bonding. To the best of our knowledge, this study introduces the first case of integrating fragments from self‐assembling molecules to design a small organic molecule that forms novel hierarchical nanotubes with polymorphism. The molecule's compact design incorporates three structural motifs derived from known nanotube assemblies, enabling a hierarchical assembly process: individual molecules with two conformations form dimers, which organize into hexameric units. These hexamers further assemble into nanotubes comprising 2‐, 5‐, and 6‐protofilament fibers. The nanofibers share a nearly identical asymmetric unit – a hexameric triangular plate – with similar axial and lateral interfaces. The lateral interface, involving interactions between phosphate groups and aromatic rings, exhibits plasticity, allowing slight rotational variations between adjacent units. This adaptability facilitates the formation of diverse nanofiber architectures, showcasing the flexibility of these systems in aqueous environments. By leveraging fragments of self‐assembling molecules, this work demonstrates a straightforward strategy that combines conformational flexibility and self‐assembling fragments to construct advanced supramolecular biomaterials from small organic building blocks in aqueous settings.
Environmental DNA Epigenetics Accurately Predicts the Age of Cultured Fish Larvae
Authors: Ruiz Eliot , Leprieur Fabien , Sposito Gérard , Lüthi Martina , Schmidlin Michel , Panfili Jacques , Pellissier Loïc , Albouy Camille 
Published: February 2025

ABSTRACTWhile acquiring age information is crucial for efficient stock management and biodiversity conservation, traditional aging methods fail to offer a universal, non‐invasive, and precise way of estimating a wild animal's age. DNA methylation from tissue DNA (tDNA) was recently proposed as a method to overcome these issues and showed more accurate results than telomere‐length‐based age assessments. Here, we used environmental DNA (eDNA) for the first time as a template for age estimation, focusing on the larval phase (10–24 days post‐hatch) of cultured Dicentrarchus labrax (seabass), a species of major economic and conservation interest. Using third‐generation sequencing, we were able to directly detect various modification types (e.g., cytosine and adenosine methylation in all contexts) across the whole genome using amplification‐free nanopore sequencing. However, aging sites were only present in the mitogenome, which could be a specific feature of eDNA methylation or the consequence of better DNA protection within mitochondria. By considering qualitative and quantitative information about aging sites according to an objective model selection framework, our epigenetic clock reached a cross‐validated accuracy of 2.6 days (Median Absolute Error). Such performances are higher than those of previous clocks, notably for adult seabass even when scaling MAE to the age range, which could be linked to a more dynamic epigenome during early life stages. Overall, our pilot study proposes new methods to determine the potential of eDNA for simultaneous age and biodiversity assessments, although robust validation of our preliminary results along with methodological developments are needed before field applications can be envisaged.