bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain
Authors: Mousa Shaaban A. , Shakibaei Mehdi , Sitte Nicolle , Schäfer Michael , Stein Christoph
Published: November 2003

The opioid peptide β-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.
Human Placental Growth Hormone Increases Expression of the P85 Regulatory Unit of Phosphatidylinositol 3-Kinase and Triggers Severe Insulin Resistance in Skeletal Muscle
Authors: Barbour Linda A. , Shao Jianhua , Qiao Liping , Leitner Wayne , Anderson Marianne , Friedman Jacob E. , Draznin Boris
Published: November 2003

The insulin resistance of normal pregnancy is necessary to divert fuels to the fetus to meet fetal growth demands and is mediated by placental hormones. We recently demonstrated that human placental GH (hPGH) can trigger severe insulin resistance in transgenic (TG) mice. In this study we sought to elucidate the cellular mechanisms by which hPGH interferes with insulin signaling in muscle in TG mice. Insulin-stimulated GLUT-4 translocation to the plasma membrane (PM) was reduced in the TG compared with wild-type (WT) mice (P = 0.05). Insulin receptor (IR) levels were modestly reduced by 19% (P < 0.01) in TG mice, but there were no changes in phosphorylation of IR or IR substrate-1 (IRS-1) between WT and TG mice. A singular finding was a highly significant increase in the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase; P < 0.001), yet a reduced ability of insulin to stimulate IRS-1-associated PI 3-kinase activity (P < 0.05). Although the levels of the p110 catalytic subunit protein of PI 3-kinase and IRS-1 were unchanged in the TG mice, insulin’s ability to stimulate p110 association with IRS-1 was markedly reduced (P < 0.0001). We demonstrate a unique mechanism of insulin resistance and suggest that hPGH may contribute to the insulin resistance of normal pregnancy by increasing the expression of the p85α monomer, which competes in a dominant negative fashion with the p85-p110 heterodimer for binding to IRS-1 protein.
Steroids and Oocyte Maturation—A New Look at an Old Story
Authors: Hammes Stephen R.
Published: November 2003

Female fertility requires precise regulation of oocyte meiosis. Oocytes are arrested early in the meiotic cycle until just before ovulation, when ovarian factors trigger meiosis, or maturation, to continue. Although much has been learned about the late signaling events that accompany meiosis, until recently less was known about the early actions that initiate maturation. Studies using the well-characterized model of transcription-independent steroid-induced oocyte maturation in Xenopus laevis now show that steroid metabolism, classical steroid receptors, G protein-mediated signaling, and novel G protein-coupled receptors, all may play important roles in regulating meiosis. Furthermore, steroids appear to promote similar events in mammalian oocytes, implying a conserved mechanism of maturation in vertebrates. Interestingly, testosterone is a potent promoter of mammalian oocyte maturation, suggesting that androgen actions in the oocyte might be partially responsible for the polycystic ovarian phenotype and accompanying infertility associated with high androgen states such as polycystic ovarian syndrome or congenital adrenal hyperplasia. A detailed appreciation of the steroid-activated signaling pathways in frog and mammalian oocytes may therefore prove useful in understanding both normal and abnormal ovarian development in humans.
TheCaenorhabditis elegans schnurrihomologsma-9mediates stage- and cell type-specific responses to DBL-1 BMP-related signaling
Authors: Liang Jun , Lints Robyn , Foehr Marisa L. , Tokarz Rafal , Yu Ling , Emmons Scott W. , Liu Jun , Savage-Dunn Cathy
Published: November 2003

In Caenorhabditis elegans, the DBL-1 pathway, a BMP/TGFβ-related signaling cascade, regulates body size and male tail development. We have cloned a new gene, sma-9, that encodes the C. elegans homolog of Schnurri, a large zinc finger transcription factor that regulates dpp target genes in Drosophila. Genetic interactions, the sma-9 loss-of-function phenotype, and the expression pattern suggest that sma-9 acts as a downstream component and is required in the DBL-1 signaling pathway, and thus provide the first evidence of a conserved role for Schnurri proteins in BMP signaling. Analysis of sma-9 mutant phenotypes demonstrates that SMA-9 activity is temporally and spatially restricted relative to known DBL-1 pathway components. In contrast with Drosophila schnurri, the presence of multiple alternatively spliced sma-9 transcripts suggests protein isoforms with potentially different cell sublocalization and molecular functions. We propose that SMA-9 isoforms function as transcriptional cofactors that confer specific responses to DBL-1 pathway activation.
Cadherin-mediated cell interaction regulates germ cell determination in mice
Authors: Okamura Daiji , Kimura Thoru , Nakano Toru , Matsui Yasuhisa
Published: November 2003

The germ cell lineage segregates from the somatic cell lineages in early embryos. Germ cell determination in mice is not regulated by maternally inherited germplasm, but is initiated within the embryo during gastrulation. However, the mechanisms of germ cell specification in mice remain unknown. We located precursors to primordial germ cells (PGCs) within early embryos, and show here that cell-cell interaction among these precursors is required for germ cell specification. We found that the expression of a calcium-dependent cell adhesion molecule, E-cadherin, is restricted to the proximal region of extra-embryonic mesoderm that contains PGC precursors, and that blocking the functions of E-cadherin with an antibody inhibits PGC formation in vitro. These results showed that E-cadherin-mediated cell-cell interaction among cells containing PGC precursors is essential to directing such cells to the germ cell fate.
AnO-fucose site in the ligand binding domain inhibits Notch activation
Authors: Lei Liang , Xu Aiguo , Panin Vladislav M. , Irvine Kenneth D.
Published: November 2003

Two glycosyltransferases that transfer sugars to EGF domains, OFUT1 and Fringe, regulate Notch signaling. However, sites of O-fucosylation on Notch that influence Notch activation have not been previously identified. Moreover, the influences of OFUT1 and Fringe on Notch activation can be positive or negative, depending on their levels of expression and on whether Delta or Serrate is signaling to Notch. Here, we describe the consequences of eliminating individual, highly conserved sites of O-fucose attachment to Notch. Our results indicate that glycosylation of an EGF domain proposed to be essential for ligand binding, EGF12, is crucial to the inhibition of Serrate-to-Notch signaling by Fringe. Expression of an EGF12 mutant of Notch(N-EGF12f) allows Notch activation by Serrate even in the presence of Fringe. By contrast, elimination of three other highly conserved sites of O-fucosylation does not have detectable effects. Binding assays with a soluble Notch extracellular domain fusion protein and ligand-expressing cells indicate that the NEGF12f mutation can influence Notch activation by preventing Fringe from blocking Notch-Serrate binding. The N-EGF12f mutant can substitute for endogenous Notch during embryonic neurogenesis, but not at the dorsoventral boundary of the wing. Thus, inhibition of Notch-Serrate binding by O-fucosylation of EGF12 might be needed in certain contexts to allow efficient Notch signaling.
Retinoic acid regulates endothelial cell proliferation during vasculogenesis
Authors: Lai Lihua , Bohnsack Brenda L. , Niederreither Karen , Hirschi Karen K.
Published: November 2003

A dietary deficiency of vitamin A is associated with cardiovascular abnormalities in avian and murine systems. Retinoic acid (RA) is the active metabolite of vitamin A and whether it directly regulates mammalian blood vessel formation has not been determined and is investigated herein. We used mice rendered RA-deficient via targeted deletion of retinaldehyde dehydrogenase 2 (Raldh2-/-), the enzyme required to produce active RA in the embryo. Histological examination at E8.0-8.5, prior to cardiac function and systemic blood circulation, revealed that capillary plexi formed in Raldh2-/- yolk sacs and embryos, but were dilated, and not appropriately remodeled or patterned. Raldh2-/- endothelial cells exhibited significantly increased expression of phosphohistone 3 and decreased expression of p21 and p27, suggesting that RA is required to control endothelial cell cycle progression during early vascular development. Uncontrolled endothelial cell growth, in Raldh2-/- mutants, was associated with decreased endothelial cell maturation, disrupted vascular plexus remodeling and lack of later stages of vessel assembly, including mural cell differentiation. Maternally administrated RA restored endothelial cell cycle control and vascular patterning. Thus, these data indicate that RA plays a crucial role in mammalian vascular development; it is required to control endothelial cell proliferation and vascular remodeling during vasculogenesis.
High-Dose Versus Standard-Dose Amoxicillin for Acute Otitis Media
Authors: Garrison Gina Daubney , Sorum Paul C , Hioe Wayne , Miller Margaret M
Published: November 2003

BACKGROUND:

Emergence of drug-resistant bacteria has led to a recommendation to use high-dose (HD) amoxicillin (80–90 mg/kg/d) rather than standard-dose (SD) amoxicillin (40–45 mg/kg/d) to treat children with acute otitis media (AOM).

OBJECTIVE:

To compare the efficacy and tolerability of HD versus SD amoxicillin among children with AOM who were considered at low risk for infection with antibiotic-resistant bacteria.

METHODS:

A double-blind, randomized, 3-year clinical trial was conducted using participants who met the following criteria: age >3 mo, weight ≤18 kg, diagnosed with AOM, and candidates for treatment with amoxicillin. The primary endpoint was treatment success at a 3- to 4-day follow-up visit based on the clinical decision to continue the prescribed antibiotic therapy for AOM. Other endpoints included duration of illness, number of office visits and telephone calls related to illness, total number of subsequent AOM episodes, and number of adverse effects.

RESULTS:

The absolute difference in antibiotic failure rate with SD versus HD amoxicillin at the follow-up visit was nonsignificant (95% CI–1.5% to 3.4%; p = 0.78). The mean duration of illness was similar for both doses of amoxicillin (3 ± 2 d). The number of office visits and telephone calls related to illness and the number of subsequent AOM episodes did not differ between the 2 treatment groups. HD amoxicillin did not result in a greater incidence of adverse effects than SD amoxicillin.

CONCLUSIONS:

HD amoxicillin had neither benefit nor detriment compared with SD for AOM in children at low risk for infection with antibiotic-resistant bacteria.
Adherence or Compliance? Changes in Terminology
Authors: Tilson Hugh H
Published: November 2003

The terminology used in healthcare-related literature has been shown to reflect not only the knowledge of the practitioners, but also their beliefs and attitudes regarding patient care. One great area of change has been the inclusion of the patient in the determination and success of therapy, with the term “adherence” seeming to indicate this action more accurately than ”compliance.” Hugh H Tilson has been practicing within the public health arena for many years and so is knowledgeable about this altered philosophy in pharmacy practice. Within this editorial, he discusses the implications of the evolution of practitioners' approach to health care. Based on these changes, we will now begin using the term “adherence” in The Annals to reflect the partnership between the healthcare provider and patient.
Building CRISPR Gene Therapies for the Central Nervous System
Authors: Salomonsson Sally E. , Clelland Claire D.
Published: January 2024

Importance

Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) holds the promise to arrest or cure monogenic disease if it can be determined which genetic change to create without inducing unintended cellular dysfunction and how to deliver this technology to the target organ reliably and safely. Clinical trials for blood and liver disorders, for which delivery of CRISPR is not limiting, show promise, yet no trials have begun for central nervous system (CNS) indications.

Observations

The CNS is arguably the most challenging target given its innate exclusion of large molecules and its defenses against bacterial invasion (from which CRISPR originates). Herein, the types of CRISPR editing (DNA cutting, base editing, and templated repair) and how these are applied to different genetic variants are summarized. The challenges of delivering genome editors to the CNS, including the viral and nonviral delivery vehicles that may ultimately circumvent these challenges, are discussed. Also, ways to minimize the potential in vivo genotoxic effects of genome editors through delivery vehicle design and preclinical off-target testing are considered. The ethical considerations of germline editing, a potential off-target outcome of any gene editing therapy, are explored. The unique regulatory challenges of a human-specific therapy that cannot be derisked solely in animal models are also discussed.

Conclusions and Relevance

An understanding of both the potential benefits and challenges of CRISPR gene therapy better informs the scientific, clinical, regulatory, and timeline considerations of developing CRISPR gene therapy for neurologic diseases.
Plasma proteomic profiles of UK Biobank participants with multiple sclerosis
Authors: Jacobs Benjamin M. , Vickaryous Nicola , Giovannoni Gavin , Proitsi Petroula , Waters Sheena , Dobson Ruth
Published: January 2024

Objective

We aimed to describe plasma protein biomarkers of multiple sclerosis risk and to explore protein biomarkers of disease severity using radiological outcome measures.

Methods

Multiple sclerosis cases and controls were identified in UK Biobank, a longitudinal cohort study of ~500,000 British adults. Plasma proteins were assayed in ~50,000 UK Biobank participants using the Olink proximity extension assay. We performed case–control association testing to examine the association between 2911 proteins and multiple sclerosis, using linear models adjusted for confounding covariates. Associations with radiological lesion burden and brain volume were determined in a subset of the cohort with available magnetic resonance imaging, using normalized T2‐hyperintensity volume or whole brain volume as the outcome measure.

Results

In total, 407 prevalent multiple sclerosis cases and 39,979 healthy controls were included. We discovered 72 proteins associated with multiple sclerosis at a Bonferroni‐adjusted p value of 0.05, including established markers such as neurofilament light chain and glial fibrillary acidic protein. We observed a decrease in plasma Granzyme A, a marker of T cell and NK cell degranulation, which was specific to multiple sclerosis. Higher levels of plasma proteins involved in coagulation were associated with lower T2 lesion burden and preserved brain volume.

Interpretation

We report the largest plasma proteomic screen of multiple sclerosis, replicating important known associations and suggesting novel markers, such as the reduction in granzyme A. While these findings require external validation, they demonstrate the power of biobank‐scale datasets for discovering new biomarkers for multiple sclerosis.
Event‐triggered model reference adaptive control system design for SISO plants using meta‐learning‐based physics‐informed neural networks without labeled data and transfer learning
Authors: Duanyai Worrawat , Song Weon Keun , Konghuayrob Poom , Parnichkun Manukid
Published: January 2024

This paper examines the controllability of a novel Lyapunov‐based model reference adaptive control (MRAC) system designed with a meta‐learning‐based physics‐informed neural network (MLPINN) for linear and nonlinear single‐input and single‐output (SISO) plants without labeled data (MLPINN‐MRAC system). It is devised with the benefits of several techniques: the integration of the identification process in a training mode into an online control mode (straightforward design); no labeled data generation for online identification by a physics‐informed neural network; the prevention of degradation in tracking performance by meta‐learning, as the system triggers a meta‐learning process only when an error threshold detects the deterioration (high efficiency and the reduction of computation cost); quick adaptation to new inputs and an updated control input for each sub‐time span by transfer learning. It is worth noting that the frequency of the meta‐learning event detection significantly affects the step response stability of the nonlinear plant. To achieve a better quality of the stabilization, more frequent event detection is necessary for both beginning and end intervals in control. Sixteen triggering events are enough to shape the acceptable step response of the nonlinear plant, and 44 triggering events achieve the plant's desired step response with its minor modeling error. While, as for the linear plant, a single triggering event is sufficient to attain its tolerable step response and modeling error, implying that intensive event detection is not critical in the identification. It is obvious that the MLPINN‐MRAC system functions well and is more beneficial and efficient for the nonlinear plant.
Hybrid Co‐Spinning and Melt Electrowriting Approach Enables Fabrication of Heterotypic Tubular Scaffolds Resembling the Non‐Linear Mechanical Properties of Human Blood Vessels
Authors: Bartolf‐Kopp Michael , de Silva Leanne , Rosenberg Antoine J. W. P. , Groll Jürgen , Gawlitta Debby , Jungst Tomasz
Published: January 2024

The current barrier to clinical translation of small‐caliber tissue‐engineered vascular grafts (TEVGs) is the long‐term patency upon implantation in vivo. Key contributors are thrombosis and stenosis caused by inadequate mechanical graft properties and mismatch of hemodynamic conditions. Herein, the authors report on an approach for the fabrication of a mechanically tunable bilayered composite TEVGs. Using a combination of solution electrospinning (SES) and melt electrowriting (MEW), it is shown that the mechanical properties can be tailored and the natural J‐shape of the stress–strain relationship can be recapitulated. Upon cell seeding, the luminal surface of the composite SES layers permits the formation of a confluent mature endothelium. MEW fibers provide structural support to promote stacking and orientation of MSCs in a near‐circumferential native vessel like direction. By adjusting the ratios of poly(ε‐caprolactone) and poly(ester‐urethane) during the SES process, TEVGs with a range of tunable mechanical properties can be manufactured. Notably, this hybrid approach permits modulation of the radial tensile properties of TEVGs to approximate different native vessels. Overall, a strategy for the fabrication of TEVGs with mechanical properties resembling those of native vessels which can help to accommodate long‐term patency of TEVGs at various treatment sites in future applications is demonstrated.
Surface Enrichment in Gallium‐Indium Liquid Alloys: Applied to CO2 Conversion
Authors: Gholampoursaadi Fahimeh , Zhi Xing , Nour Shirin , Liu Jefferson Zhe , Li Gang Kevin , Mayyas Mohannad
Published: January 2024

Liquid metal alloys can accumulate specific solute metal atoms on their surface, creating distinct quasi‐ordered atomic layers. Such atomic layers can be tuned by varying the alloy composition to form catalytic interfaces suited for multi‐step reactions. Here, the surface enrichment in gallium‐indium alloys is studied and utilized for carbon dioxide (CO2) electrochemical reduction. The results show that adding a small amount of indium (16.8 at%) to gallium leads to a significant indium enrichment of >83 at% on the topmost layer of the alloy. This enrichment dictates the CO2 conversion pathway, leading to 98% faradaic efficiency toward formate at −1.90 V vs reversible hydrogen electrode (RHE). This study produces unprecedented insights into key interfacial processes and lays the foundation for significant further work within the areas of catalysis and liquid metals.
Tailoring Ultra‐Wide Visible‐NIR Luminescence by Ce3+/Cr3+/Yb3+‐alloying Sc‐Based Oxides for Multifunctional Optical Applications
Authors: Zhang Min , Dang Peipei , Wan Yujia , Wang Yingsheng , Zeng Zixun , Liu Dongjie , Zhang Qianqian , Li Guogang , Lin Jun
Published: January 2024

Visible‐to‐near‐infrared (VIS‐NIR) luminescent materials are in great demand in the field of non‐destructive testing such as component determination and hyperspectral imaging. Although Cr3+‐activated phosphors are widely reported, controllable tailoring ultra‐wide VIS‐NIR luminescence excited by blue light is still a challenge. The strategies of cationic substitution and energy transfers are effective for adjusting the luminescence of Cr3+‐activated phosphors. In this work, a series of Cr3+‐doped Sc‐based solid solution phosphors (Ba3‐mSrmSc4O9:Cr3+) are reported. Under the excitation of blue light, these phosphors exhibit broadband emission due to the different luminescence centers induced by Cr3+ occupying different cationic sites. Because of the weaker crystal field strength, Cr3+ realizes a broadband emission with a longer peak position (λem = 820 nm) and broader full width at half maximum (FWHM≈182 nm) in Ba2SrSc4O9. Furthermore, Ce3+/Yb3+ ions are introduced into Ba2SrSc4O9:Cr3+, achieving an ultra‐wide VIS‐NIR luminescence (460–1200 nm) by the Ce3+→Cr3+→Yb3+ multiple energy transfers. Designing energy transfers is beneficial to improve the quantum efficiency and weaken the thermal quenching. Finally, the NIR phosphor‐converted light‐emitting diode (pc‐LED) fabricated by Ba2SrSc4O9:Cr3+ demonstrates great potential in night‐vision and water component detection. This work provides an effective design idea for controllable tailoring ultra‐wide VIS‐NIR luminescence by chemical substitution and energy transfer.
Enhancing Stability and Efficacy of Trichoderma Bio‐Control Agents Through Layer‐by‐Layer Encapsulation for Sustainable Plant Protection
Authors: Løvschall Kaja Borup , Velasquez Sara T. R. , Kowalska Beata , Ptaszek Magdalena , Jarecka Anna , Szczech Magdalena , Wurm Frederik R.
Published: January 2024

Agricultural fungicide pollution poses a significant environmental challenge and causes adverse effects on human health. Therefore, strategies to limit fungicide usage are of paramount importance. Trichoderma fungi, due to their antagonistic activity against various pathogenic fungi, have shown potential as a sustainable alternative to chemical fungicides. However, bio‐control agents like Trichoderma are vulnerable to physical stimuli and show diminished efficacy during prolonged storage. To address these challenges, a mild and scalable encapsulation method for Trichoderma spores is introduced, employing a layer‐by‐layer (LbL) approach using biobased lignin derivatives. It is demonstrated that the LbL encapsulation technique significantly improved spore stability relative to naked spores, even under adverse conditions including extreme temperatures and prolonged exposure to Ultraviolet (UV) irradiation. Notably, encapsulated Trichoderma spores showed enhanced efficacy in cultivating tomato plants compared to naked spores. Additionally, the findings revealed that the in planta efficacy of encapsulated spores is dependent on the specific Trichoderma strain used. This study suggests that Trichoderma spores encapsulated with lignin through the LbL approach, are a promising and sustainable alternative to chemical fungicides with potential for commercialization.
Proximity Sensing Electronic Skin: Principles, Characteristics, and Applications
Authors: Wu Bingwei , Jiang Ting , Yu Zhongxiang , Zhou Qihui , Jiao Jian , Jin Ming Liang
Published: January 2024

The research on proximity sensing electronic skin has garnered significant attention. This electronic skin technology enables detection without physical contact and holds vast application prospects in areas such as human‐robot collaboration, human‐machine interfaces, and remote monitoring. Especially in the context of the spread of infectious diseases like COVID‐19, there is a pressing need for non‐contact detection to ensure safe and hygienic operations. This article comprehensively reviews the significant advancements in the field of proximity sensing electronic skin technology in recent years. It covers the principles, as well as single‐type proximity sensors with characteristics such as a large area, multifunctionality, strain, and self‐healing capabilities. Additionally, it delves into the research progress of dual‐type proximity sensors. Furthermore, the article places a special emphasis on the widespread applications of flexible proximity sensors in human‐robot collaboration, human‐machine interfaces, and remote monitoring, highlighting their importance and potential value across various domains. Finally, the paper provides insights into future advancements in flexible proximity sensor technology.
High‐Reproducibility Layer‐by‐Layer Non‐Fullerene Organic Photovoltaics with 19.18% Efficiency Enabled by Vacuum‐Assisted Molecular Drift Treatment
Authors: Xie Yongchao , Zhou Chunyu , Ma Xiaoling , Jeong Sang Young , Woo Han Young , Huang Fulong , Yang Yiyi , Yu Haomiao , Li Jinpeng , Zhang Fujun , Wang Kai , Zhu Xixiang
Published: January 2024

The thin film deposition engineering of layer‐by‐layer (LbL) non‐fullerene organic solar cells (OSCs) favors vertical phase distributions of donor:acceptor (D:A), effectively boosting the power conversion efficiency (PCE). However, previous deposition strategies mainly aimed at optimizing the morphology of LbL films, and paid limited attention to the reproducibility of device performance. To achieve high device performance and maintain reproducibility, a strategy for hierarchical morphology manipulation in LbL OSCs is developed. A series of LbL devices are fabricated by introducing vacuum‐assisted molecular drift treatment (VMDT) to the donor or acceptor layer individually or simultaneously to elucidate the functionalities of this treatment. Essentially, the VMDT provides an extended drift driving force to manipulate the donor and acceptor molecules, resulting in a well‐defined vertical phase distribution and ordered molecular packing. These enhancements facilitate improvement in the D:A interface area and charge transport channel, ultimately contributing to impressive PCEs of 19.18% from 18.27% in the LbL devices. More importantly, using VMDT overcomes the notorious batch‐dependent and heat treatment degradation issues of OSCs, leading to excellent batch‐to‐batch reproducibility and enhanced stability of the devices. This reported method provides a promising strategy available for industrial and laboratory use to controllably manipulate the morphology of LbL OSCs.
Scientific activism to protect the world's primates and their environments from extinction: Introduction to the special issue
Authors: Garber Paul A. , Dolins Francine , Lappan Susan
Published: January 2024

Nonhuman primates and their habitats are facing an impending extinction crisis. Approximately 69% of primate species are listed by the International Union for Conservation of Nature as threatened and 93% have declining populations. Human population growth (expected to reach 10.9 billion by the year 2100), the unsustainable demands of a small number of consumer nations for forest‐risk commodities, deforestation and habitat conversion, the expansion of roads and rail networks, cattle ranching, the hunting and trapping of wild primate populations, and the potential spread of infectious diseases are among the primary drivers of primate population decline. Climate change will only exacerbate the current situation. The time to act to protect primate populations is now! In this special issue of the American Journal of Primatology, we present a series of commentaries, formulated as “Action Letters.” These are designed to educate and inform primatologists, conservation biologists, wildlife ecologists, political leaders, and global citizens about the conservation challenges faced by particular primate taxa and particular world regions, and present examples of specific actions that one can take, individually and collectively, to promote the persistence of wild primate populations and environmental justice for local human populations and impacted ecological communities. As scientists, researchers, and educators, primatologists are in a unique position to lead local, national, and international efforts to protect biodiversity. In this special issue, we focus on primates of the Brazilian Amazon, lemurs of northeast Madagascar, Temminck's red colobus monkey (Piliocolobus badius temminckii), night monkeys (Aotus spp.), long‐tailed macaques (Macaca fascicularis), the primate pet trade, and professional capacity building to foster conservation awareness and action. We encourage primatologists, regardless of their research focus, to engage in both advocacy and activism to protect wild primate populations worldwide.
Cross‐national comparisons of later‐life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices
Authors: Kobayashi Lindsay C. , Jones Richard N. , Briceño Emily M. , Rentería Miguel Arce , Zhang Yuan , Meijer Erik , Langa Kenneth M. , Lee Jinkook , Gross Alden L.
Published: January 2024

The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross‐national comparisons of later‐life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross‐national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high‐quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.
Metal–Phenolic‐Mediated Assembly of Functional Small Molecules into Nanoparticles: Assembly and Bioapplications
Authors: Chen Jingqu , Cortez‐Jugo Christina , Kim Chan‐Jin , Lin Zhixing , Wang Tianzheng , De Rose Robert , Xu Wanjun , Wang Zhaoran , Gu Yuang , Caruso Frank
Published: January 2024

Small molecules, including therapeutic drugs and tracer molecules, play a vital role in biological processing, disease treatment and diagnosis, and have inspired various nanobiotechnology approaches to realize their biological function, particularly in drug delivery. Desirable features of a delivery system for functional small molecules (FSMs) include high biocompatibility, high loading capacity, and simple manufacturing processes, without the need for chemical modification of the FSM itself. Herein, we report a simple and versatile approach, based on metal–phenolic‐mediated assembly, for assembling FSMs into nanoparticles (i.e., FSM‐MPN NPs) under aqueous and ambient conditions. We demonstrate loading of anticancer drugs, latency reversal agents, and fluorophores at up to ~80 % that is mostly facilitated by π and hydrophobic interactions between the FSM and nanoparticle components. Secondary nanoparticle engineering involving coating with a polyphenol–antibody thin film or sequential co‐loading of multiple FSMs enables cancer cell targeting and combination delivery, respectively. Incorporating fluorophores into FSM‐MPN NPs enables the visualization of biodistribution at different time points, revealing that most of these NPs are retained in the kidney and heart 24 h post intravenous administration. This work provides a viable pathway for the rational design of small molecule nanoparticle delivery platforms for diverse biological applications.
Boosting the π‐Acceptor Property of Mesoionic Carbenes by Carbonylation with Carbon Monoxide
Authors: Merschel Arne , Vishnevskiy Yury V. , Neumann Beate , Stammler Hans‐Georg , Ghadwal Rajendra S.
Published: January 2024

We report the room temperature dimerization of carbon monoxide mediated by C4/C5‐vicinal anionic dicarbenes Li(ADC) (ADC = ArC{(Dipp)NC}2; Dipp = 2,6‐iPr2C6H3; Ar = Ph, DMP (4‐Me2NC6H4), Bp (4‐PhC6H4)) to yield (E)‐ethene‐1,2‐bis(olate) (i.e. −O−C=C−O− = COen) bridged mesoionic carbene (iMIC) lithium compounds COen‐[(iMIC)Li]2 (COen‐[iMIC]2 = [ArC{(Dipp)NC}2(CO)]2) in quantitative yields. COen‐[(iMIC)Li]2 are highly colored stable solids, exhibit a strikingly small HOMO–LUMO energy gap, and readily undergo 2e‐oxidations with selenium, CuCl (or CuCl2), and AgCl to afford the dinuclear compounds COon‐[(iMIC)E]2 (E = Se, CuCl, AgCl) featuring a 1,2‐dione bridged neutral bis‐iMIC (i.e. COon‐[iMIC]2 = [ArC{(Dipp)NC}2(C=O)]2). COen‐[(iMIC)Li]2 undergo redox‐neutral salt metathesis reactions with LiAlH4 and (Et2O)2BeBr2 and afford COen‐[(iMIC)AlH2]2 and COen‐[(iMIC)BeBr]2, in which the dianionic COen‐moiety remains intact. All compounds have been characterized by NMR spectroscopy, mass spectrometry, and X‐ray diffraction. Stereoelectronic properties of COon‐[iMIC]2 are quantified by experimental and theoretical methods.
Beyond waste: Transforming wheat straw into oxygen and UV‐resistant cellulose films
Authors: Tang Yali , Han Penghong , Lu Lixin , Qiu Xiaolin , Pan Liao
Published: January 2024

Regenerated cellulose membrane is a biomaterial obtained by activating, dissolving, solidifying, and regenerating cellulose powder using solvents of different polarities. It has the characteristics of high oxygen resistance and high strength. However, its low water vapor barrier and single function limit its application. In order to improve the water resistance of regenerated cellulose membranes and endow them with UV resistance, lignin was extracted from waste wheat straw using formic acid method. The extracted formic acid lignin (FAL) was added to the cellulose solution to prepare a series of regenerated lignocellulosic membranes (RC‐FAL) with different lignin contents. The results indicate that lignin can not only improve the water vapor barrier, tensile strength, and water resistance of the film, but also enhance the oxygen barrier and UV absorption of the film. Compared with pure cellulose film, the contact angle of lignocellulose film can be increased by 66.2%, the UV absorption rate can reach 100%, and the oxygen transmission coefficient has no significant effect. In this paper, a new kind of biological packaging material with high oxygen resistance, strong ultraviolet absorption, and water resistance was prepared by recycling waste wheat straw, it has a broad application prospect in the industrial production of packaging materials.
Effect of terminal substituent of iso‐indigo‐based materials on the intermolecular stacking and memory performance
Authors: Hu Haiyan , Zhang Yong , Qin Hongni , Guan Weijia , Fang Menghan , Zhang Cheng , Li Yang
Published: January 2024

Attributed to the characteristics of narrow band gap structural units and full spectral response, iso‐indigo is often used as an electron acceptor in organic electronic materials. Organic molecules with large conjugated surfaces and strong intermolecular forces can form ordered stacked structures through self‐assembly. In this paper, the self‐assembly performances of IDCF3 and IDCN are regulated by changing the end groups. The effects of terminal groups on the resistive memory behaviours and reproducibility are investigated. The properties of IDCF3 and IDCN devices are characterized by UV‐VIS spectroscopy, cyclic voltammetry and DSC diffraction. The results show that when the end groups with different steric hindrance are introduced into the ends of the molecules with good backbone plane, the conjugated surfaces of the molecules will bend due to the different steric hindrance of the end groups in the form of cambium and layer‐ordered packing, which will affect the threshold voltage and device reproducibility.
Predefined‐time adaptive fuzzy tracking control for switched nonlinear systems
Authors: Jin Yitong , Wang Fang , Zhao Maoxian
Published: January 2024

The paper focuses on the issue of predefined‐time adaptive fuzzy tracking control for switched nonlinear systems. The complicated unknown nonlinear function is approximated by utilizing the fuzzy logic system. A novel adaptive fuzzy control scheme is proposed by using the common Lyapunov function and backstepping technology on the basis of the definition of predefined‐time stability, which can preset the setting time of tracking errors. The findings indicate that the presented controller can ensure that all signals remain bounded in the closed‐loop system under arbitrary switching conditions, and the tracking error can converge to the neighborhood near the origin within a predefined time. The feasibility of the developed control approach is further proved through an example of numerical simulation.
Predicting survival in patients with buccal cancer: A study based on SEER database and external validation in China
Authors: Tan Yongmei , Huang Guoxing , Hu Jintao , Zhao Shaoping , Li Yanyan , Wen Zhihui , Wang Liansheng , Chen Suling , Chen Rongxi , Cao Haotian , Li Jinsong
Published: January 2024

Objective

Buccal mucosa cancer (BMC) is one of the most common oral cancers and has poor prognosis. The study aimed to develop and validate nomograms for predicting the 1‐, 3‐, and 5‐year overall survival (OS) and cancer‐specific survival (CSS) of BMC patients.

Methods

We collected and reviewed information on BMC patients diagnosed between 2004 and 2019 from the Surveillance Epidemiology and End Results database. Two nomograms were developed and validated to predict the OS and CSS based on predictors identified by univariate and multivariate Cox regression. An extra external validation was further performed using data from Sun Yat‐sen Memorial Hospital (SYSMH).

Results

A total of 3154 BMC patients included in this study were randomly assigned to training and validation groups in a 2:1 ratio. Independent prognostic predictors were identified, confirmed, and fitted into nomograms for OS and CSS, respectively. The C‐indices are 0.767 (Training group OS), 0.801 (Training group CSS), 0.763 (Validation group OS), and 0.781 (Validation group OS), respectively. Moreover, the nomograms exhibited remarkable precision in forecasting and significant clinical significance, as evidenced by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). The final validation using our data from SYSMH also showed high accuracy and substantial clinical benefits within the nomograms. The C‐indices are 0.849 (SYSMH group OS) and 0.916 (SYSMH group CSS). These indexes are better than tumor, node, and metastasis stage based on prediction results.

Conclusions

The nomograms developed with great performance predicted 1‐, 3‐, and 5‐year OS and CSS of BMC patients. Use of the nomograms in clinical practices shall bring significant benefits to BMC patients.
Individuals' materialism and brand rituals and traditions as drivers of luxury brand love on social media
Authors: Cruz‐Ros Sonia , Miquel‐Romero Maria‐Jose , Yee Rachel W. Y.
Published: January 2024

Luxury brands have engaged in social media use, becoming exposed to a wider market but confronting the exclusivity and uniqueness linked to these brands. This paper explores the role of a personality trait and a brand characteristic in brand love by social media users in the luxury fashion industry. Specifically, the individual's materialism (measured by the relevance given to luxury premium prices and fashionability), the essence of the brand perceived through its rituals and traditions, and their influence on self–brand integration are considered. An empirical study is carried out on 432 social media users, and two different research methodologies are conducted: Partial Least Squares Structural Equation Modelling (PLS‐SEM) and fuzzy‐set Qualitative Comparative Analysis (fsQCA). Findings from both methodologies support the relevance of the variables analysed with regard to brand love. However, fsQCA offers a new perspective by identifying that for loving the brand, materialistic individuals also have to value the brand's rituals and traditions; and that personality traits can contribute to brand love, the resultant outcome of the relevance given to a luxury premium price, or to its aesthetic and fashionability, but not to both aspects at the same time; finally, self–brand integration is not necessary for brand love but is sufficient. From these results, managerial implications are suggested in order to favour brand love, as it exerts a strong influence on purchase intention.
Synthesis of Amino Acid‐Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery
Authors: Mandal Subhasis , Mallik Suman , Bhoumick Avinandan , Bhattacharya Anindita , Sen Prosenjit
Published: January 2024

Leveraging liposomes for drug and nucleic acid delivery, though promising due to reduced toxicity and ease of preparation, faces challenges in stability and efficiency. To address this, we synthesized cationic amphiphiles from amino acids (arginine, lysine, and histidine). Histidine emerged as the superior candidate, leading to the development of three histidine‐rich cationic amphiphiles for liposomes. Using the hydration method, we have prepared the liposomes and determined the optimal N/P ratios for lipoplex formation via gel electrophoresis. In vitro transfection assays compared the efficacy of our lipids to Fugene, while MTT assays gauged biocompatibility across cancer cell lines (MDA‐MB 231 and MCF‐7). The histidine‐based lipid demonstrated marked potential in enhancing drug and nucleic acid delivery. This improvement stemmed from increased zeta potential, enhancing electrostatic interactions with nucleic acids and cellular uptake. Our findings underscore histidine‘s crucial role over lysine and arginine for effective delivery, revealing a significant correlation between histidine abundance and optimal performance. This study paves the way for histidine‐enriched lipids as promising candidates for efficient drug and nucleic acid delivery, addressing key challenges in the field.
The Impact of Activating Agents on Non‐Enzymatic Nucleic Acid Extension Reactions
Authors: Callaghan Kimberley L. , Sherrell Peter C. , Ellis Amanda V.
Published: January 2024

Non‐enzymatic template‐directed primer extension is increasingly being studied for the production of RNA and DNA. These reactions benefit from producing RNA or DNA in an aqueous, protecting group free system, without the need for expensive enzymes. However, these primer extension reactions suffer from a lack of fidelity, low reaction rates, low overall yields, and short primer extension lengths. This review outlines a detailed mechanistic pathway for non‐enzymatic template‐directed primer extension and presents a review of the thermodynamic driving forces involved in entropic templating. Through the lens of entropic templating, the rate and fidelity of a reaction are shown to be intrinsically linked to the reactivity of the activating agent used. Thus, a strategy is discussed for the optimization of non‐enzymatic template‐directed primer extension, providing a path towards cost‐effective in vitro synthesis of RNA and DNA.
Performance evaluation of maltogenic amylases on nixtamalized corn flour tortilla
Authors: Leung Sophia , Go Angel Lene , Keo Malissa , Al‐Ammar Assad , Roda Dipak , Rathi Vic
Published: January 2024

Background and Objectives

A high‐performing maltogenic amylase was developed to provide better water‐binding properties to delay staling more effectively than first‐generation maltogenic amylases. This study evaluated the effects of this high‐performing maltogenic amylase and a first‐generation maltogenic amylase (referred to as “maltogenic amylase”) for delaying staling in nixtamalized corn flour tortillas. The maltogenic amylase and high‐performing maltogenic amylase were tested at 25, 50, and 100 ppm and were compared to control tortillas.

Findings

Tortillas with 100 ppm high‐performing maltogenic amylase were 66% softer and performed better in foldability than control tortillas after 35 days of room temperature storage and rated better in taste and tenderness than the control.

Conclusions

Both maltogenic amylases delayed staling and prolonged softness and foldability.

Significance and Novelty

Overall, the high‐performing maltogenic amylase did not outperform the first‐generation maltogenic amylase at 25 and 50 ppm. However, at a higher dosage (100 ppm), the high‐performing maltogenic amylase is capable of producing overall softer tortillas with improved tenderness and taste across 35 days of storage. This research is novel as this high‐performing maltogenic amylase has not been studied by others to improve the quality of tortillas.
Identifying causative medications for agranulocytosis: A case report of an older adult with cerebral infarction
Authors: Kurokawa Yuuri , Watanabe Ayako , Kashiwabara Yuka , Fukuda Saori , Nomoto Shohei , Kuriki Ayako , Momo Kenji
Published: January 2024

Key Clinical Message

Most drugs that cause adverse events are difficult to identify in critically ill patients undergoing polypharmacy. We share our experience in identifying the causative drug among four suspect drugs administered during emergency treatment.

We present the case of a 93‐year‐old man who was admitted for the treatment of cerebrovascular events. The patient was initially prescribed dual antiplatelet therapy with aspirin and clopidogrel along with lansoprazole, Hange‐koboku‐toh, and elobixibat. On day 36 after admission, the patient was found to have developed agranulocytosis. To improve his cerebrovascular prognosis, we first discontinued medications other than the anticoagulant medicines and initiated filgrastim. We discontinued clopidogrel 9 days after the discontinuation of the other medicines considering his low white blood cell count. One day after the discontinuation of clopidogrel, the agranulocytosis was alleviated. Considering the time course, clopidogrel, lansoprazole, Hange‐koboku‐toh, and elobixibat were suspected as the culprit medicines. This case highlights the considerable challenges encountered in clinical practice when attempting to identify the drugs responsible for agranulocytosis, particularly in patients on intensive medication therapy.