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Drawing upon the literatures in information privacy, developmental psychology, and family science, this research investigates how parental online privacy concerns can be passed on to adolescents and affect their self-disclosure on social networking sites. We propose that parental privacy concerns decrease adolescents' self-disclosure both directly (i.e., compliance) and indirectly through adolescents' privacy concerns (i.e., internalization) and that such effects are moderated by parent-child privacy dissonance, parental internet evaluative mediation, and adolescents' gender. To test the research model, we collected matched parent-child data from 726 families in China. The results show the indirect effect of parental privacy concerns on adolescents' self-disclosure via their influence on adolescents' privacy concerns. In addition, parent-child privacy dissonance weakens the effect of adolescents' privacy concerns on selfdisclosure. The extent to which parents employ internet evaluative mediation to guide adolescents' online activities reinforces the effect of parental privacy concerns on adolescents' privacy concerns. Statistical analyses further revealed that the mediating effect of adolescents' privacy concerns is weakened by parent-child privacy dissonance but strengthened by internet evaluative mediation. We also found that parental privacy concerns affect sons and daughters through different paths, especially when parents employ high internet evaluative mediation. Under high internet evaluative mediation, parental privacy concerns affect sons' self-disclosure primarily through an indirect path (via sons' privacy concerns), but influence daughters' self-disclosure both directly and indirectly via daughters' privacy concerns. We conclude by discussing theoretical contributions and practical implications. [ABSTRACT FROM AUTHOR]

BamA, an Omp85 superfamily member, is universally conserved and essential for cell viability. Using anti‐Oma87 antibodies, we focus on understanding the effect of Oma87 of Acinetobacter baumannii on pathogenicity. Oma87 was expressed, purified, and used to induce anti‐Oma87 antibodies in BALB/c mice. Acute toxicity of the protein was evaluated in mice. HeLa cells were infected with both live and killed A. baumannii 19606 and a clinical isolate. The effects of anti‐Oma87 sera on A. baumannii adherence, internalization, and proliferation in HeLa cells were studied. The roles of microfilaments and microtubules in A. baumannii invasion were demonstrated by Actin disruption. Reduced bacterial population and biofilm formation were noted. The ability of A. baumannii to provoke autophagy through Oma87 induction leads to incomplete autophagy and potentially facilitates bacterial replication. Actin‐mediated uptake, attachment, and invasion demonstrated A. baumannii survival and multiplication within vacuoles in the host cell. The findings underscore the potential of Oma87 as a therapeutic intervention target in infections caused by A. baumannii. This comprehensive analysis contributes valuable information for understanding the virulence mechanisms of A. baumannii, potentially guiding future strategies to combat infections caused by this pathogen. [ABSTRACT FROM AUTHOR]

Introduction: Visceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the phagocytes and the parasite is crucial to determine the pathogen's capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1β, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-β) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/ Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1- dependent activation. Objective and methods: Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures. Results: Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-β production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response. Discussion and conclusion: These data corroborate the hypothesis that MR1- restricted responses are associated to a protective role during Leishmania infection. [ABSTRACT FROM AUTHOR]

Background: The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. Methods: In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. Results: We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. Conclusion: Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain. [ABSTRACT FROM AUTHOR]

This work investigated the influence of surface chirality on cellular internalization, cytotoxicity, and tissue distribution of silver nanoparticles (AgNPs). D-cysteine and L-cysteine are chiral forms of the amino acid cysteine. These enantiomers exhibit distinct spatial arrangements, with D-cysteine having a different configuration from L-cysteine. This structural dissimilarity can lead to variations in how these forms interact with biological systems, potentially impacting their cytotoxic responses. Four distinct types of AgNPs were synthesized, each possessing a unique surface coating: pristine AgNPs (pAgNPs), L-cysteine coated AgNPs (AgNPs@L-Cys), D-cysteine coated AgNPs (AgNPs@D-Cys), and racemic AgNPs coated with both L-Cys and D-Cys (AgNPs@L/D-Cys). We found chiral-dependent cytotoxicity of AgNPs on J774A.1 cells. Specifically, AgNPs@L-Cys exhibited the highest toxicity, and AgNPs@D-Cys exhibited the lowest toxicity. Meanwhile, the cellular uptake of the AgNPs correlated nicely with their cytotoxicity, with AgNPs@L-Cys being internalized to the greatest extent while AgNPs@D-Cys displays the least internalization. Scavenger receptors and clathrin predominantly mediate the cellular internalization of these AgNPs. Strikingly, the dissimilar cellular internalization and cytotoxicity of AgNPs with different chirality were eliminated upon protein corona coverage. Notably, following intravenous injection in mice, these four types of AgNPs showed similar patterns among various organs due to the inevitable protein adsorption in the bloodstream. These findings underscored the pivotal role of surface chirality in governing the biological interactions and toxicity of AgNPs. • Chiral-dependent cytotoxicity of AgNPs on J774A.1 cells was found. • Cellular uptake of the AgNPs correlated with their cytotoxicity. • Protein corona eliminated the chirality of AgNPs. • Four types of AgNPs showed similar tissue distribution pattern. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusions and Implications The gut hormone glucose‐dependent insulinotropic polypeptide (GIP) signals via the GIP receptor (GIPR), resulting in postprandial potentiation of glucose‐stimulated insulin secretion. The translation of results from rodent studies to human studies has been challenged by the unexpected effects of GIPR‐targeting compounds. We, therefore, investigated the variation between species, focusing on GIPR desensitization and the role of the receptor C‐terminus.The GIPR from humans, mice, rats, pigs, dogs and cats was studied in vitro for cognate ligand affinity, G protein activation (cAMP accumulation), recruitment of beta‐arrestin and internalization. Variants of the mouse, rat and human GIPRs with swapped C‐terminal tails were studied in parallel.The human GIPR is more prone to internalization than rodent GIPRs. Despite similar agonist affinities and potencies for Gαs activation, especially, the mouse GIPR shows reduced receptor desensitization, internalization and beta‐arrestin recruitment. Using an enzyme‐stabilized, long‐acting GIP analogue, the species differences were even more pronounced. ‘Tail‐swapped’ human, rat and mouse GIPRs were all fully functional in their Gαs coupling, and the mouse GIPR regained internalization and beta‐arrestin 2 recruitment properties with the human tail. The human GIPR lost the ability to recruit beta‐arrestin 2 when its own C‐terminus was replaced by the rat or mouse tail.Desensitization of the human GIPR is dependent on the C‐terminal tail. The species‐dependent functionality of the C‐terminal tail and the different species‐dependent internalization patterns, especially between human and mouse GIPRs, are important factors influencing the preclinical evaluation of GIPR‐targeting therapeutic compounds. [ABSTRACT FROM AUTHOR]

Micropterus salmoides rhabdovirus (MSRV) is an important pathogen of largemouth bass. Despite extensive research, the functional receptors of MSRV remained unknown. This study identified the host protein, laminin receptor (LamR), as a cellular receptor facilitating MSRV entry into host cells. Our results demonstrated that LamR directly interacts with MSRV G protein, playing a pivotal role in the attachment and internalization processes of MSRV. Knockdown of LamR with siRNA, blocking cells with LamR antibody, or incubating MSRV virions with soluble LamR protein significantly reduced MSRV entry. Notably, we found that LamR mediated MSRV entry via clathrinmediated endocytosis. Additionally, our findings revealed that MSRV G and LamR were internalized into cells and co-localized in the early and late endosomes. These findings highlight the significance of LamR as a cellular receptor facilitating MSRV binding and entry into target cells through interaction with the MSRV G protein. IMPORTANCE Despite the serious epidemic caused by Micropterus salmoides rhabdovirus (MSRV) in largemouth bass, the precise mechanism by which it invades host cells remains unclear. Here, we determined that laminin receptor (LamR) is a novel target of MSRV, that interacts with its G protein and is involved in viral attachment and internalization, transporting with MSRV together in early and late endosomes. This is the first report demonstrating that LamR is a cellular receptor in the MSRV life cycle, thus contributing new insights into host-pathogen interactions. [ABSTRACT FROM AUTHOR]

The sodium–potassium pump (NKA) or Na+/K+ ATPase consumes around 30–40% of the total energy expenditure of the animal cell on the generation of the sodium and potassium electrochemical gradients that regulate various electrolyte and nutrient transport processes. The vital role of this protein entails proper spatial and temporal regulation of its activity through modulatory mechanisms involving its expression, localization, enzymatic activity, and protein–protein interactions. The residence of the NKA at the plasma membrane is compulsory for its action as an antiporter. Despite the huge body of literature reporting on its trafficking between the cell membrane and intracellular compartments, the mechanisms controlling the trafficking process are by far the least understood. Among the molecular determinants of the plasma membrane proteins trafficking are intrinsic sequence-based endocytic motifs. In this review, we (i) summarize previous reports linking the regulation of Na+/K+ ATPase trafficking and/or plasma membrane residence to its activity, with particular emphasis on the endocytic signals in the Na+/K+ ATPase alpha-subunit, (ii) map additional potential internalization signals within Na+/K+ ATPase catalytic alpha-subunit, based on canonical and noncanonical endocytic motifs reported in the literature, (iii) pinpoint known and potential phosphorylation sites associated with NKA trafficking, (iv) highlight our recent studies on Na+/K+ ATPase trafficking and PGE2-mediated Na+/K+ ATPase modulation in intestine, liver, and kidney cells. [ABSTRACT FROM AUTHOR]

While all reversible receptor-targeting radioligands for positron emission tomography (PET) can be displaced by competition with an antagonist at the receptor, many radiotracers show limited occupancies using agonists even at high doses. [11C]Raclopride, a D2/D3 receptor radiotracer with rapid kinetics, can identify the direction of changes in the neurotransmitter dopamine, but quantitative interpretation of the relationship between dopamine levels and radiotracer binding has proven elusive. Agonist-induced receptor desensitization and internalization, a homeostatic mechanism to downregulate neurotransmitter-mediated function, can shift radioligand-receptor binding affinity and confound PET interpretations of receptor occupancy. In this study, we compared occupancies induced by amphetamine (AMP) in drug-naive wild-type (WT) and internalization-compromised β-arrestin-2 knockout (KO) mice using a within-scan drug infusion to modulate the kinetics of [11C]raclopride. We additionally performed studies at 3 h following AMP pretreatment, with the hypothesis that receptor internalization should markedly attenuate occupancy on the second challenge, because dopamine cannot access internalized receptors. Without prior AMP treatment, WT mice exhibited somewhat larger binding potential than KO mice but similar AMP-induced occupancy. At 3 h after AMP treatment, WT mice exhibited binding potentials that were 15 % lower than KO mice. At this time point, occupancy was preserved in KO mice but suppressed by 60 % in WT animals, consistent with a model in which most receptors contributing to binding potential in WT animals were not functional. These results demonstrate that arrestin-mediated receptor desensitization and internalization produce large effects in PET [11C]raclopride occupancy studies using agonist challenges.

Abstract Background The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. Methods In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. Results We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. Conclusion Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.

Siân Rizzo,1 Mathieu Varache,1 Edward J Sayers,2 Arwyn T Jones,2 Alex Tonks,3 David W Thomas,1 Elaine L Ferguson1 1Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, UK; 2School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 3Department of Haematology, School of Medicine, Cardiff University, Cardiff, UKCorrespondence: Elaine L Ferguson, Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, UK, Tel +44 2922 510663, Email FergusonEL@cardiff.ac.ukIntroduction: Acute myeloid leukemia (AML) remains difficult to treat due to its heterogeneity in molecular landscape, epigenetics and cell signaling alterations. Precision medicine is a major goal in AML therapy towards developing agents that can be used to treat patients with different ‘subtypes’ in combination with current chemotherapies. We have previously developed dextrin–colistin conjugates to combat the rise in multi-drug resistant bacterial infections and overcome dose-limiting nephrotoxicity. Recent evidence of colistin’s anticancer activity, mediated through inhibition of intracellular lysine-specific histone demethylase 1 (LSD1/KDM1A), suggests that dextrin–colistin conjugates could be used to treat cancer cells, including AML. This study aimed to evaluate whether dextrin conjugation (which reduces in vivo toxicity and prolongs plasma half-life) could enhance colistin’s cytotoxic effects in myeloid leukemia cell lines and compare the intracellular uptake and localization of the free and conjugated antibiotic.Results: Our results identified a conjugate (containing 8000 g/mol dextrin with 1 mol% succinoylation) that caused significantly increased toxicity in myeloid leukemia cells, compared to free colistin. Dextrin conjugation altered the mechanism of cell death by colistin, from necrosis to caspase 3/7-dependent apoptosis. In contrast, conjugation via a reversible ester linker, instead of an amide, had no effect on the mechanism of the colistin-induced cell death. Live cell confocal microscopy of fluorescently labelled compounds showed both free and dextrin-conjugated colistins were endocytosed and co-localized in lysosomes, and increasing the degree of modification by succinoylation of dextrin significantly reduced colistin internalization.Discussion: Whilst clinical translation of dextrin–colistin conjugates for the treatment of AML is unlikely due to the potential to promote antimicrobial resistance (AMR) and the relatively high colistin concentrations required for anticancer activity, the ability to potentiate the effectiveness of an anticancer drug by polymer conjugation, while reducing side effects and improving biodistribution of the drug, is very attractive, and this approach warrants further investigation. Keywords: polymer therapeutics, biodegradable, internalization, polysaccharide, antibiotic

Abstract Bovine lactoferrin (bLF) is a glycosylated protein with purported beneficial properties. The aim of this work was to determine the role of bLF glycosylation in the adhesion, internalization, and growth inhibition of cancer cells. The viability of cervix (HeLa) and colon (Caco‐2) cancer cells (MTT assay and epifluorescence microscopy) was inhibited by bLF, while deglycosylated bLF (bLFdeg) had no effect. Adhesion to cell surfaces was quantified by immunofluorescence assay and showed that bLF was able to bind more efficiently to both cell lines than bLFdeg. Microscopic observations indicated that bLF glycosylation favored bLF binding to epithelial cells and that it was endocytosed through caveolin‐1‐mediated internalization. In addition, the mechanism of action of bLF on cancer cell proliferation was investigated by determining the amount of phosphorylated intermediates of signaling pathways such as epidermal growth factor receptor (EGFR), extracellular signal‐regulated kinase (ERK) and protein kinase B (known as Akt). Chemoluminescence immunoassay of phosphorylated intermediates showed that bLF inhibited Akt phosphorylation, consistent with its growth inhibiting activity. This assay also indicated that the bLF receptor/signaling pathways may be different in the two cell lines, Caco‐2 and HeLa. This work confirmed the effect of glycosylated bLF in inhibiting cancer cell growth and that glycosylation is required for optimal surface adhesion, internalization, and inhibition of the ERK/Akt pathway of cell proliferation through glycosylated cell surface receptors.

Shailey Gale Twamley,1– 3 Niclas Gimber,4 Héctor Eduardo Sánchez-Ibarra,1,2 Tobias Christaller,1,2 Victoria Isakzai,1,2 Harald Kratz,5 Ronodeep Mitra,6 Lena Kampen,1– 3 Anke Stach,1,2 Heike Heilmann,7 Berit Söhl-Kielczynski,8 Eno Essien Ebong,6,9,10 Jan Schmoranzer,4 Agnieszka Münster-Wandowski,7,* Antje Ludwig1– 3,* 1Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany; 2Department of Cardiology, Angiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; 3DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; 4Advanced Medical Bioimaging Core Facility (AMBIO), Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 5Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 7Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 8Institute for Integrative Neurophysiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 9Department of Bioengineering, Northeastern University, Boston, MA, USA; 10Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA*These authors contributed equally to this workCorrespondence: Shailey Gale Twamley; Antje Ludwig, Tel +49-30-450-528455 ; +49-30-450-513196, Fax +49-30-450-528922 ; +49-30-450941, Email shailey.twamley@charite.de; antje.ludwig@dhzc-charite.dePurpose: To study whether the absence of laminar shear stress (LSS) enables the uptake of very small superparamagnetic iron oxide nanoparticles (VSOP) in endothelial cells by altering the composition, size, and barrier function of the endothelial surface layer (ESL).Methods and Results: A quantitative particle exclusion assay with living human umbilical endothelial cells using spinning disc confocal microscopy revealed that the dimension of the ESL was reduced in cells cultivated in the absence of LSS. By combining gene expression analysis, flow cytometry, high pressure freezing/freeze substitution immuno-transmission electron microscopy, and confocal laser scanning microscopy, we investigated changes in ESL composition. We found that increased expression of the hyaluronan receptor CD44 by absence of shear stress did not affect the uptake rate of VSOPs. We identified collagen as a previously neglected component of ESL that contributes to its barrier function. Experiments with inhibitor halofuginone and small interfering RNA (siRNA) demonstrated that suppression of collagen expression facilitates VSOP uptake in endothelial cells grown under LSS.Conclusion: The absence of laminar shear stress disturbs the barrier function of the ESL, facilitating membrane accessibility and endocytic uptake of VSOP. Collagen, a previously neglected component of ESL, contributes to its barrier function. Keywords: citrate coated nanoparticles, atherosclerosis, blood flow, endothelial barrier, permeability, internalization

Project management and project portfolio management (PPM) foster competitiveness by facilitating the implementation of organizational strategy. Although organizations often struggle to develop PPM capabilities, the academic community does not have an in-depth understanding of the conditions for successfully developing these capabilities. In response, we conducted a multiple-case study with 50 interviewees to develop a theoretical model of the PPM capability-building process. This model is built on the notion of organizational sensemaking and identifies aspects that comprehensively explain why it usually takes so long to develop PPM capabilities. We conceptualize the PPM capability-building process as one that is strongly influenced by (1) the effects of structural rearrangements, (2) the appropriate use of external resources during that process, (3) the role of executive support and legitimization, (4) episodes of regression, and (5) the need for internalization and habitualization. In addition, we provide starting points for explaining organizational capability building in more general terms. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy. Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy. [ABSTRACT FROM AUTHOR]

0D biomaterials (0DBMs) can serve as carriers to enhance and extend the regulatory effects of biological cues they transport on cell fate via bacterial/mammalian cell internalization. However, accurately delivering and amplifying biosignals through 0DBMs remains challenging to cope with ecological niche destabilization induced by factors such as trauma or infection. Herein, the "zero‐dimensional amplification" approach is employed to develop a surface carboxylate carbon dot (CQD‐COOH) conjugated with a neutrophil constitutive peptide (LL‐37), resulting in the formation of a 0D peptide quantum dot (LQD). Hydrogel‐released LQDs, when internalized by bacteria, cause the bacteria to programmatically rupture and die, whereas LQDs internalized by mesenchymal stem cells (MSCs) activate the cellular CXCL12/CXCR4 signaling axis, which directs the stem cells to homing and anchor to the surface of the hydrogel coating. Notably, this strategy of "zero‐dimensional amplification" enables the antimicrobial performance of LL‐37 to be boosted approximately 1.3‐fold, significantly extending the transmission efficiency of biosignals. Meanwhile, 0D lipid nanoparticles (lipo‐NPs) with targeting function incorporated into the hydrogel could deliver the bio‐small molecule MK‐4 to MCSs and induce their endocytosis, further enhancing osseointegration. Thus, the hydrogel coating (HGLL) under this strategy can significantly remodel the ecological niche of the implant–bone interface in infected environment. [ABSTRACT FROM AUTHOR]

Vaspin is a serine protease inhibitor that protects against adipose tissue inflammation and insulin resistance, two key drivers of adipocyte dysfunction and metabolic disorders in obesity. Inhibition of target proteases such as KLK7 has been shown to reduce adipose tissue inflammation in obesity, while vaspin binding to cell surface GRP78 has been linked to reduced obesity‐induced ER stress and insulin resistance in the liver. However, the molecular mechanisms by which vaspin directly affects cellular processes in adipocytes remain unknown. Using fluorescently labeled vaspin, we found that vaspin is rapidly internalized by mouse and human adipocytes, but less efficiently by endothelial, kidney, liver, and neuronal cells. Internalization occurs by active, clathrin‐mediated endocytosis, which is dependent on vaspin binding to the LRP1 receptor, rather than GRP78 as previously thought. This was demonstrated by competition experiments and RNAi‐mediated knock‐down in adipocytes and by rescuing vaspin internalization in LRP1‐deficient Pea13 cells after transfection with a functional LRP1 minireceptor. Vaspin internalization is further increased in mature adipocytes after insulin‐stimulated translocation of LRP1. Although vaspin has nanomolar affinity for LRP1 clusters II‐IV, binding to cell surface heparan sulfates is required for efficient LRP1‐mediated internalization. Native, but not cleaved vaspin, and also vaspin polymers are efficiently endocytosed, and ultimately targeted for lysosomal degradation. Our study provides mechanistic insight into the uptake and degradation of vaspin in adipocytes, thereby broadening our understanding of its functional repertoire. We hypothesize the vaspin‐LRP1 axis to be an important mediator of vaspin effects not only in adipose tissue but also in other LRP1‐expressing cells. [ABSTRACT FROM AUTHOR]

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•−, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 μg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the identity development and internalization of an asexual orientation and how asexual individuals attempt to reject and resist societal attitudes held towards their orientation. Participants were recruited through the online community the Asexuality Visibility and Education Network (AVEN) and included five women between the ages of 18 and 40. Data were gathered using semi-structured interviews and analyzed using interpretative phenomenological analysis (IPA). Five themes emerged from the data: The Asexual Self, Discovering Asexuality, Disclosure, Navigating Relationships and Barriers to Accepting Asexuality. The development of an asexual identity was initiated through an awareness of the self as different within society and supported by external resources such as the online asexual community. Although all participants described a sense of pride surrounding their asexual identity, some participants at times attempted to minimize the importance of asexuality to their self-concepts. Social norms and the values of a heteronormative society influenced participants' abilities to accept their orientation, as well as their coming-out processes. There were notable discrepancies between participants' accounts that were specific to their romantic orientation and age. The theoretical implications of each theme within the development of an asexual identity and internalization of an asexual orientation are discussed. This research outlines the process of developing an asexual identity including an awareness of the self as different, active searching, finding a community and coming-out. These findings inform our understanding of how asexual individuals develop a positive sense of self and come to accept their lack of sexual desire. [ABSTRACT FROM AUTHOR]

Among the theoretical contributions made by Hans Loewald, some of the most meaningful address the developmental process of differentiation from a primary or original unity into "id-ego and objects." This differentiation requires "separation, loss, and restitution," and results in a shift from oneness/unity to at-onement, a connection that bears within it the trace of the separation it emends. A parallel dynamic plays out in the shift from identification to internalization in Loewald's work. The author identifies this dynamic as cohering difference, a structural interaction in both intra- and inter-psychic processes graphically illustrated by the hyphen in Loewald's concept of "at-onement." The author examines these processes and the significance of cohering difference, illustrated by Loewald's idea of "linking," and presents a clinical example in which loss, grief, identification, and internalization play key roles. [ABSTRACT FROM AUTHOR]

Instructional shifts required by equitable, reform‐based science instruction are challenging, especially in the elementary context. Such shifts require professional development (PD) that supports teacher internalization of new pedagogical strategies as well as changes in beliefs about how students learn. Because of this complexity, many PD programs struggle to foster lasting pedagogical shifts, necessitating further investigation into why some teachers successfully embrace reform practices while others do not. This qualitative study uses a nonlinear, iterative model of teacher learning (Interconnected Model of Professional Growth; Clarke & Hollingsworth, 2002) alongside professional noticing to help understand why elementary teachers in science PD differentially make sense of and internalize new pedagogies. Findings indicate that teachers most likely to adopt reform‐based instructional practices from the PD were those who clearly connected student learning to their instructional moves. In addition, teachers who more actively attended to student sensemaking and productive struggle took up pedagogies from the PD more substantively than did colleagues who attended solely to student engagement and affect. Finally, teachers who attended to and valued novel ideas from students' lived experiences were more likely to change their beliefs about students' capacity to learn science, and thus more likely to see the value of instructional practices from the PD. In sum, structuring PD to build on these specific teacher noticing skills can encourage more teachers to move away from traditional, teacher‐directed instructional practice, and more fully support reform‐based instructional practices. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF) is a glycosylated protein with purported beneficial properties. The aim of this work was to determine the role of bLF glycosylation in the adhesion, internalization, and growth inhibition of cancer cells. The viability of cervix (HeLa) and colon (Caco‐2) cancer cells (MTT assay and epifluorescence microscopy) was inhibited by bLF, while deglycosylated bLF (bLFdeg) had no effect. Adhesion to cell surfaces was quantified by immunofluorescence assay and showed that bLF was able to bind more efficiently to both cell lines than bLFdeg. Microscopic observations indicated that bLF glycosylation favored bLF binding to epithelial cells and that it was endocytosed through caveolin‐1‐mediated internalization. In addition, the mechanism of action of bLF on cancer cell proliferation was investigated by determining the amount of phosphorylated intermediates of signaling pathways such as epidermal growth factor receptor (EGFR), extracellular signal‐regulated kinase (ERK) and protein kinase B (known as Akt). Chemoluminescence immunoassay of phosphorylated intermediates showed that bLF inhibited Akt phosphorylation, consistent with its growth inhibiting activity. This assay also indicated that the bLF receptor/signaling pathways may be different in the two cell lines, Caco‐2 and HeLa. This work confirmed the effect of glycosylated bLF in inhibiting cancer cell growth and that glycosylation is required for optimal surface adhesion, internalization, and inhibition of the ERK/Akt pathway of cell proliferation through glycosylated cell surface receptors. [ABSTRACT FROM AUTHOR]

The aim of this paper is to give an account of what it is to internalize a rule. I claim that internalization is the process of redistributing the burden of instruction from the teacher to the student. The process is complete when instruction is no longer needed, and the rule has reshaped perceptual classification of the circumstances in which it applies. Teaching a rule is the initiation of this process. We internalize rules by simulating instruction coming from someone else. Running these simulations enables us to toggle between the perspective of the instructor and our own perspective. By doing this we coordinate our perspectives with that of the teacher. The account given here provides a deeper explanation of why internalizing a rule involves the dispositions and reactive attitudes proponents of Rule Consequentialism often say it does, why moral reflection is variably demanding, how intergenerational moral progress is made possible by our cognitive architectures, and why the adoption of a rule should be understood in terms of teaching that rule. [ABSTRACT FROM AUTHOR]

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization. [ABSTRACT FROM AUTHOR]

IntroductionImmunogenicity, the unwanted immune response triggered by therapeutic antibodies, poses significant challenges in biotherapeutic development. This response can lead to the production of anti-drug antibodies, potentially compromising the efficacy and safety of treatments. The internalization of therapeutic antibodies into dendritic cells (DCs) is a critical factor influencing immunogenicity. Using monoclonal antibodies, with differences in non-specific cellular uptake, as tools to explore the impact on the overall risk of immunogenicity, this study explores how internalization influences peptide presentation and subsequently T cell activation.Materials and methodsTo investigate the impact of antibody internalization on immunogenicity, untargeted toolantibodies with engineered positive or negative charge patches were utilized. Immature monocyte-derived DCs (moDCs), known for their physiologically relevant high endocytic activity, were employed for internalization assays, while mature moDCs were used for MHC-II associated peptide proteomics (MAPPs) assays. In addition to the lysosomal accumulation and peptide presentation, subsequent CD4+ T cell activation has been assessed. Consequently, a known CD4+ T cell epitope from ovalbumin was inserted into the tool antibodies to evaluate T cell activation on a single, shared epitope.ResultsAntibodies with positive charge patches exhibited higher rates of lysosomal accumulation and epitope presentation compared to those with negative charge patches or neutral surface charge. Furthermore, a direct correlation between internalization rate and presentation on MHC-II molecules could be established. To explore the link between internalization, peptide presentation and CD4+ T cell activation, tool antibodies containing the same OVA epitope were used. Previous observations were not altered by the insertion of the OVA epitope and ultimately, an enhanced CD4+ T cell response correlated with increased internalization in DCs and peptide presentation.DiscussionThese findings demonstrate that the biophysical properties of therapeutic antibodies, particularly surface charge, play a crucial role in their internalization into DCs. Antibodies internalized faster and processed by DCs, are also more prone to be presented on their surface leading to a higher risk of triggering an immune response. These insights underscore the importance of considering antibody surface charge and other properties that enhance cellular accumulation during the preclinical development of biotherapeutics to mitigate immunogenicity risks.

The aim of this research is to determine the extent of internalization of spiritual values in shaping students' religious character. This research uses a qualitative approach. The subjects of this research were teachers and students at SMAN 1 Kartasura. This research was carried out from October to December 2023 with the informants in this research namely the school principal, Islamic religious education teacher, and students. Meanwhile, data collection was carried out through observation, interviews and documentation. Data analysis was carried out using data reduction, data presentation and data verification. The results show that spiritual values are internalized through habituation before PAI lessons, Friday prayers and mentoring. Meanwhile, the supporting factors are habituated and religious week. The inhibiting factors are internal factors. Internal factors inhibiting the formation of students' religious character are age and psychological factors. External factors are under the influence of the family environment, school environment and of course the community environment.

The lungs are commonly targeted by Acinetobacter baumannii. The human alveolar basal epithelial cell line, A549, serves as a valuable in vitro model for probing pathogen-cell dynamics. This study examined two Acinetobacter strains, ATCC 19606 and the clinical isolate 58ST, investigating their adherence, internalization, and cytotoxicity within the A549 cell line to illuminate pathogenic mechanisms. Anti-BamA antibodies were expressed, purified, and detected via indirect ELISA. The toxicity of BamA was assessed across BALB/c mice. Both A. baumannii strains were used to infect A549 cells to scrutinize cell invasion diversity. Serum resistance, biofilm creation and inhibition, adhesion, internalization, and intracellular proliferation of live and inactivated A. baumannii were probed with and without anti-BamA sera. A549 cell viability was evaluated in the presence of live A. baumannii and anti-BamA sera-exposed bacteria. Cytoskeleton inhibitor tests were conducted on epithelial cells. A. baumannii strains displayed differing cell invasion aptitudes, with the clinical variant manifesting the highest invasion capability. During internalization, A. baumannii cells localized within vacuoles and migrated towards the nucleus using a zipper-like invasion mechanism. Bacterial division inside host cells culminated in cell demise. Pre-treatment with anti-BamA antibodies substantially impeded A. baumannii's adherence and invasion in epithelial cells. Microscopic imaging validated the intracellular presence of A. baumannii in A549 cells, verifying their invasive potential and residency. These findings substantiate A. baumannii's capacity to proliferate in epithelial cells, with BamA pivotal role against A. baumannii-epithelial cell interplay. This study augments our insight into A. baumannii pathogenesis, facilitating the development of efficacious strategies against A. baumannii infections.

Background. Theory of mind is the capacity to explain and predict the behavior of others. Charles Fernyhough’s dialogical model of psychological functions offers a vision of theory of mind that considers the social dimension and the importance of language, especially inner and private speech, for a person’s ability to represent and manipulate multiple perspectives, and its connection to executive function. Objective. There is little direct research on Fernyhough’s model. The present study addressed that gap by studying the relationship between theory of mind, private speech, and executive function (planning) in the preschool years. Design. Data were collected from a total of 86 preschool children from the Mexican state of Tlaxcala; 24 were from the first grade of preschool, 30 from the second, and 32 from the third. Their degree of internalization and their speech types (i.e., social and private) were obtained by coding their utterances during free play and during performance of a Tower of London task. Lastly, their theory of mind was assessed with a change of location and an unexpected contents task. Results. No correlation was found between children’s theory of mind and their degree of internalization. However, inaudible private speech was correlated (negatively) to theory of mind performance in the third grade of preschool. Furthermore, their scores on the Tower of London task were negatively correlated with social speech and positively correlated with inaudible private speech, while the reverse was true for time of execution. Conclusion. The results suggested that the degree of internalization is a measure of the regulative function of language, not the ability to manipulate perspectives, and that it is inadequate for capturing subtle differences between performance and speech types. Role-playing conditions were recommended as better tasks for exploring the capacities for manipulating and understanding different perspectives during the preschool years.

The article reveals the content of one of the components of knowledge management – knowledge generation in an organization. An attempt is being made to identify the mechanism of this generation and to reveal the potential for its effectiveness. It is shown that knowledge for an organization has the status of a special resource: it has its own dynamics of emergence and requires specific management actions. The experience of Japanese companies is used in applying a four-phase spiral model of new knowledge formation in an organization, when knowledge is translated into real technologies and products. Creating new knowledge literally means “reshaping the company and each of its employee in a continuous process of personal and organizational selfrenewal”. The study presents the “ba” platform, which is interpreted as a system in which knowledge is activated as a creative resource and as a context in which interaction between explicit and tacit knowledge develops in a spiral. A SECI model is proposed. It describes such methods of knowledge transformation. By addressing organized processes such as knowledge creation and exchange, the mechanisms that ensure the transfer of knowledge in organizations are analyzed. It is concluded that knowledge transfer is a kind of key to a rare opportunity to understand what the prerequisites for a company competitive advantages are. A mechanism for resolving this paradoxical situation can only be formed by managers representing the creative class.

Abstract Background Weight-related stigma and discrimination are prevalent in our society with adverse biopsychosocial outcomes to people with obesity and morbid obesity. Studies suggest that weight bias in healthcare settings are quite prevalent, but there have been, as far as we know, lack of studies examining prevalence and correlates of weight bias experiences among bariatric surgery candidates in Israel. We aim to understand the nature and prevalence of weight stigma among bariatric surgery candidates. To identify differences between Jewish and Arab candidates. To examine the impact of weight stigma experiences on weight bias internalization (WBI). Methods A cross-sectional study was performed among 117 adult bariatric surgery candidates from three hospitals in northern Israel (47.8% Jews, 82.4% females, average BMI 42.4 ± 5.2 Kg/meter2). Patients who agreed to participate completed a structured questionnaire on the same day that the bariatric surgery committee met. WBI was measured using a validated 10-item scale. Experiences of weight stigma were measured using items adapted from prior international studies. Results About two thirds of the participants had at least one experience of weight stigma (teased, treated unfairly, or discriminated against because of their weight). As many as 75% of participants reported that weight served as a barrier to getting appropriate health care and as many as half of participants felt in the last year that a doctor judged them because of their weight. No significant differences were found between Arabs and Jews in the prevalence of weight stigma experiences and WBI. However, a trend towards more stigma experiences among Jews was noted. WBI was predicted by female gender and experiences of weight stigma, both in general and within healthcare settings. Conclusions Weight stigma towards bariatric surgery candidates in Israel is quite prevalent, and specifically in healthcare settings. It is important to adopt policy actions and intervention programs to improve awareness to this phenomenon among the general public and specifically among healthcare providers, as many healthcare providers may be unaware of the adverse effect of weight stigma and of ways in which they are contributing to the problem. Future studies may validate our findings using larger sample size and longitudinal design.

Cell-penetrating peptides (CPPs) are invaluable tools for delivering various substances into cells by crossing biological membranes. However, the effects of cell-penetrating peptide fusion proteins on the biological activity of antibodies remain to be fully understood. Here, we engineered a recombinant protein, LP-scFv, which combines the single-chain variable region of anti-human epidermal growth factor receptor-2 with a novel and non-oxic cell-penetrating peptide as a leader peptide. The introduction of this leader peptide led to a more than twofold increase in the internalization efficiency of the single-chain antibody, as confirmed using microscopic analysis and flow cytometry. The effects of the single-chain antibodies and LP-scFv on cell viability were evaluated using the MTT assay. Both the single-chain antibodies and LP-scFv reduced the viability of BT474 and NCI-N87 cells in a dose-dependent manner while exhibiting minimal toxicity towards MCF-7 and MCF-10A cells. Further investigation into LP-scFv's mechanism revealed that the induced leader peptide does not alter the MAPK-ERK1/2 and PI3K/AKT pathways of single-chain antibodies. An enhanced antitumor activity was also confirmed in an NCI-N87 tumor xenograft model in mice with a reduction of 45.2% in tumor growth inhibition (vs. 23.1% for scFv) with a 50 mg/kg dose after orthotopic injection administration, which was equivalent to that of trastuzumab (vs. 55.7% for trastuzumab). Overall, these results indicate that LP-scFv exhibits significant permeation activity in HER2-positive cells to enhance the intracellular dose effect on antitumor activity in vitro and in vivo. This research lays the foundation for designing novel antibody-based therapies for cancer. [ABSTRACT FROM AUTHOR]

Much of the work on body image socialization masks the potentially unique influence of different socializers, yet clearer understanding of socialization mechanisms and ideological context aid intervention efforts. We explored how fathers, female peers, male peers, and adolescent boys themselves produce different levels of internalized appearance-related norms and how these socializer-specific norms differentially relate to wellbeing and beliefs related to gender identity. With a sample of early adolescent boys (n = 260; M age = 11.44 years, SD age =.56, 64% White), we used SEM to investigate relations between internalized norms, wellbeing, and gender beliefs. We found that most boys internalized appearance-related norms, and that boys reported higher levels of norms from themselves than from fathers or peers. Internalized appearance-related norms from different socializers uniquely related to self-esteem, private/public regard of gender, and self-presentation expectations in peer interactions. This relational framework provides unique insights into boys' experiences with their appearance and the role of different socializers. [ABSTRACT FROM AUTHOR]

Various bacterial species form a microbiome in the skin. In the past, dead Staphylococcus aureus derived from atopic dermatitis (AD) are taken up by keratinocytes; however, whether live S. aureus can be taken up by keratinocytes is unknown. This study aimed to examine whether live AD strains of S. aureus internalize into the keratinocytes and how the internalization changes under conditions in which other bacterial species including S. epidermidis are present. HaCaT cells were cultured with live S. aureus and S. epidermidis (live or heat-treated) or their culture supernatants. After coculture, the change in the amount of S. aureus in the cytoplasm of HaCaT cells was analyzed using, a high-throughput imaging system, Opera Phenix™. Live S. aureus were taken up in the cytoplasm of HaCaT cells. Coculturing live S. aureus with live S. epidermidis or the culture supernatants decreased the abundance of S. aureus in the cytoplasm. The heat-treated culture supernatants of live S. epidermidis or culture supernatants of other S. strains did not decrease the abundance of S. aureus in the cytoplasm. Live S. aureus was internalized into the cytoplasm of HaCaT cells as does heat-treated S. aureus. In addition, the heat-sensitive substances secreted by coculture with S. epidermidis and keratinocytes inhibited the uptake of S. aureus by keratinocytes. • HaCaT cells internalized live AD strains of Staphylococcus (S.) aureus. • The coexistence of S. epidermidis inhibits uptake of S. aureus into HaCaT cells. • Co-culture supernatant with S. epidermidis and HaCaT cells inhibits the uptake. • S. epidermidis alone does not inhibit uptake of S. aureus. • The factors that inhibit the uptake of S. aureus are inactivated by heat treatment. [ABSTRACT FROM AUTHOR]

Background: The high frequency of eating disorders (EDs) in sports speaks of a need for early‐stage preventive measures. Objectives: This study evaluated the acceptability of an age, sex, and sports adapted version of the "Body Project" and changes in mental health symptoms. Methods: This noncontrolled pilot study included a class of athletes from 18 sports (N = 73, 13–14 years) at a sport‐specialized junior high school in six small‐group workshops. We interviewed 34 athletes on program acceptability, and all athletes responded to questionnaires at pretest, posttest, and 6‐month follow‐up including the Body Appreciation Scale 2–Children, Social Attitudes towards Appearance Questionnaire‐4 revised, Eating Disorder Examination Questionnaire Short form‐12 modified, and questions about body appearance pressure (BAP). Results: Athletes found the program acceptable and beneficial, but some missed physically oriented activities or did not identify with the focus, particularly boys. There were acceptable levels in mental health constructs before the workshops. There were temporary changes in the percentage of boys experiencing "BAP in society" by −14.8% points (95% CI: −.6 to.0, p =.04), % in total group experiencing "BAP at school" by +11% points (95% CI:.0–.2, p =.05), thinness idealization by girls (g =.6, p =.002) and total group (g =.4, p =.006), and muscularity idealization by boys (g =.3, p =.05) and total group (g =.23, p =.04). Discussion: Athletes experienced benefits from the Young Athlete Body Project. Seeing stabilization in outcomes may mean a dampening of the otherwise expected worsening in body appreciation and ED symptoms over time. Public Significance: Adolescent athletes are at risk for developing EDs. Due to lack of prevention programs for this group, we adapted and evaluated a well‐documented effective program, the Body Project, to fit male and female athletes <15 years. The athletes accepted the program and experienced participation benefits, with stronger acceptance among girls. Our promising findings encourage larger scaled randomized controlled trials to further evaluate a refined version this program among very young athletes. [ABSTRACT FROM AUTHOR]

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This article extends Bylund's theory of the firm by considering how internalization results not only in the combination of assets required for entrepreneurial innovation but also in the merging of the data streams they generate into a unified view. I argue that because data is not generally amenable to aggregation through market transactions, economies of scale in analysis imply that the informational resources required for the efficient use of local knowledge will typically only be available within the firm, which will have access to insights that would be unavailable to a collection of individuals each controlling only a subset of its physical and human capital resources. The firm may thus be viewed as an institution for facilitating observation that supersedes the individual transactor as the essential market participant. A further implication is that advances in information technology have the potential to expand optimal firm boundaries and extend firm longevity by increasing the firm's ability to derive information from the signals observed by its members. [ABSTRACT FROM AUTHOR]

Nanoparticle-based delivery systems have emerged as powerful tools in the field of pest management, offering precise and effective means of delivering double-stranded RNA (dsRNA), a potent agent for pest control through RNA interference (RNAi). This comprehensive review aims to evaluate and compare various types of nanoparticles for their suitability in dsRNA delivery for pest management applications. The review begins by examining the unique properties and advantages of different nanoparticle materials, including clay, chitosan, liposomes, carbon, gold and silica. Each material's ability to protect dsRNA from degradation and its potential for targeted delivery to pests are assessed. Furthermore, this review delves into the surface modification strategies employed to enhance dsRNA delivery efficiency. Functionalization with oligonucleotides, lipids, polymers, proteins and peptides is discussed in detail, highlighting their role in improving stability, cellular uptake, and specificity of dsRNA delivery.This review also provides valuable guidance on choosing the most suitable nanoparticle-based system for delivering dsRNA effectively and sustainably in pest management. Moreover, it identifies existing knowledge gaps and proposes potential research directions aimed at enhancing pest control strategies through the utilization of nanoparticles and dsRNA. [ABSTRACT FROM AUTHOR]

This paper explores the impact of ethical philosophies on developing an authentic leader's internalized moral perspective. It builds on prior research on moral identity, proposing that ethical philosophies such as deontology, rule utilitarianism, and virtue can be internalized over time to form an authentic leader's internalized moral identity. The paper argues that while virtues and altruism are discussed in the authentic leadership literature, the relevance of other ethical philosophies to authentic leadership has been largely overlooked. These ethical philosophies embedded in business settings can be internalized and become integral to the content of a leader's moral identity rather than merely being lenses for moral reasoning. Authentic leaders' moral identities regulate their moral motivation and actions. In addition, the paper posits that internalized ethical philosophies can be activated by triggering events or changing the domain of moral issues. Authentic leaders with highly internalized moral identities are also encouraged to be morally modest, reflecting on different ethical philosophies when facing new challenges and internalizing them as needed while staying committed to their virtue-centric moral identity. This interdisciplinary paper proposes a framework and presents theoretical propositions to further understand the role of ethical philosophies in shaping an authentic leader's internalized moral perspective. [ABSTRACT FROM AUTHOR]

Background: The Islamic boarding school as a place of education and study of Islamic sciences, is also a place for developing the character of students. One of these efforts is through internalizing the values of Islamic education in the book of Bidayat al Hidayah to develop the religious character of students. Purpose: The purpose of this study is to analyze the Program, Process, Evaluas, Supporting and inhibiting factors of the impact of internalizing Islamic educational values in the book of Bidayat al Hidayah to develop the religious character of students in Islamic boarding schools. Method: The method used in this study is the descriptive-analytical method. Results: The results showed that the internalization program of Islamic educational values in the book of Bidayat al Hidayah in Islamic boarding schools was carried out through creed formation programs, worship formation and moral formation. By indicators of having a wise attitude, courageous, maintaining self-chastity and fairness. Conclusion: Based on the results of the study, it can be concluded that the internalization program of Islamic educational values in the book of Bidayat al Hidayah consists of a creed formation program, a worship formation program and a moral formation program. [ABSTRACT FROM AUTHOR]

Bacterial biofilms, enigmatic communities of microorganisms enclosed in an extracellular matrix, still represent an open challenge in many clinical contexts, including orthopedics, where biofilm-associated bone and joint infections remain the main cause of implant failure. This study explores the scenario of biofilm infections, with a focus on those related to orthopedic implants, highlighting recently emerged substantial aspects of the pathogenesis and their potential repercussions on the clinic, as well as the progress and gaps that still exist in the diagnostics and management of these infections. The classic mechanisms through which biofilms form and the more recently proposed new ones are depicted. The ways in which bacteria hide, become impenetrable to antibiotics, and evade the immune defenses, creating reservoirs of bacteria difficult to detect and reach, are delineated, such as bacterial dormancy within biofilms, entry into host cells, and penetration into bone canaliculi. New findings on biofilm formation with host components are presented. The article also delves into the emerging and critical concept of immunometabolism, a key function of immune cells that biofilm interferes with. The growing potential of biofilm metabolomics in the diagnosis and therapy of biofilm infections is highlighted, referring to the latest research. [ABSTRACT FROM AUTHOR]