Wetlands are sources and sinks for nanoplastics (NPs), where adsorption and uptake by plants constitute a crucial pathway for NPs accumulation. This study found that Sphagnum exhibited a high potential (~89.75 %) to intercept NPs despite the lack of root systems and stomata. Two pathways for 100nm polystyrene NPs accumulation in Sphagnum were located: (i) Spiral interception and foliar adsorption. Efficient adsorption is credited to the micro/nano-interlocked leaf structure, which is porous, hydrophilic and rough. (ii) Intracellular enrichment through pores. Fluorescence tracking indicates pseudo-leaves (lateral > cephalic branches) as primary organs for internalization. Accumulation of differently functionalized NPs was characterized: PS-Naked-NPs (PS), PS-COOH-NPs (PC) and PS-NH2-NPs (PN) were all largely retained by pathway (i), while pathway (ii) mainly uptake PN and PC. Unlike PS aggregation in transparent cells, PC enrichment in chloroplast cells and PN in intercellular spaces reduced pigment content and fluorescence intensity. Further, the effects of the accumulated NPs on the ecological functions of Sphagnum were evaluated. NPs reduce carbon flux (assimilation rate by 57.78 %, and respiration rate by 33.50%), significantly decreasing biomass (PS = 13.12 %, PC = 26.48 %, PN = 35.23 %). However, toxicity threshold was around 10 μg/mL, environmental levels (≤1 μg/mL) barely affected Sphagnum. This study advances understanding of the behavior and fate of NPs in non-vascular plants, and provides new perspectives for developing Sphagnum substrates for NPs interception.

Currently, antibody drugs targeting programmed cell death ligand 1 (PD-L1) have achieved promising results in cancer treatment, while the development of small-molecule drugs lags behind. In this study, we designed and synthesized a series of PD-L1-degrading agents based on the PROTAC design principle, utilizing the PD-L1 inhibitor A56. Through systematic screening of ligands and linkers and investigating the structure-activity relationship of the degraders, we identified two highly active compounds, 9i and 9j. These compounds enhance levels of CD4+, CD8+, granzyme B, and perforin, demonstrating significant in vivo antitumor effects with a tumor growth inhibition (TGI) of up to 57.35 %. Both compounds facilitate the internalization of PD-L1 from the cell surface and promote its degradation through proteasomal and lysosomal pathways, while also maintaining inhibition of the PD-1/PD-L1 interaction. In summary, our findings provide a novel strategy and mechanism for developing biphenyl-based PROTAC antitumor drugs targeting and degrading PD-L1.

BACKGROUND: Weight stigma (devaluation due to body weight) in healthcare is common and influences one\'s engagement in healthcare, health behaviors, and relationship with providers. Positive patient-provider relationships (PPR) are important for one\'s healthcare engagement and long-term health.
OBJECTIVE: To date, no research has yet investigated whether weight bias internalization (self-stigma due to weight; WBI) moderates the effect of weight stigma on the PPR. We predict that weight stigma in healthcare is negatively associated with (i) trust in physicians, (ii) physician empathy, (iii) autonomy and competence when interacting with physicians, and (iv) perceived physician expertise. We also predict that those with high levels of WBI would have the strongest relationship between experiences of weight stigma and PPR outcomes.
METHODS: We recruited women (N = 1,114) to complete a survey about weight stigma in healthcare, WBI and the previously cited PPR outcomes.
RESULTS: Weight stigma in healthcare and WBI were associated with each of the PPR outcomes when controlling for age, BMI, education, income, race, and ethnicity. The only exception was that WBI was not associated with trust in physicians. The hypothesis that WBI would moderate the effect of weight stigma in healthcare on PPR outcomes was generally not supported.
CONCLUSIONS: Overall, this research highlights how weight stigma in healthcare as well as one\'s own internalization negatively impact PPRs, especially how autonomous and competent one feels with their provider which are essential for one to take an active role in their health and healthcare.
Being treated differently because of your weight is common in healthcare. Being treated poorly because of one’s weight when interacting with physicians can influence whether they make appointments with their doctors, how they eat, and how they interact with doctors in the future. This is important because the relationship one has with their doctor impacts their health. We expected that negative experiences with doctors about weight would impact whether people trust doctors, think their doctor is empathetic, think their doctor is an expert, and think they can be themselves around their doctor. We also expected this to be impacted by how people feel about their own body weight. 1,114 women completed a questionnaire about all these topics. Negative experiences with doctors about weight and thinking poorly of their own weight were associated with each of the expected outcomes. The only exception is that the way one felt about their own body was not associated with trusting doctors. Also, the way people felt about their own weight did not impact the effect that negative experiences had on these outcomes. Overall, this study shows how important feelings and conversations about weight are when interacting with one’s doctor.

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.

Previous research examined the role of identity confusion and body dissatisfaction in eating disorder symptoms, but an integrative perspective including identity synthesis and positive body image is lacking. The current study used three-wave longitudinal data (T1: N = 403; 52.1% female; Mage = 14.85, SD = 0.89) spanning two years to examine the directionality of effects among identity, internalization of appearance ideals, body image, and eating disorder symptoms, with attention to adaptive mechanisms. Results revealed a maladaptive pathway in which internalizing appearance ideals posed a risk for body dissatisfaction and eating disorder symptoms. Conversely, an adaptive pathway highlighted the potential protective role of positive body image regarding identity formation and internalization of appearance ideals. This study provides further insight into the critical role of appearance ideal internalization in the development of eating disorders and the potential value of positive body image. Future research and prevention/intervention efforts should focus on promoting resilience to appearance ideal internalization and enhancing positive body image in the context of identity struggles and eating disorder symptoms.

Drug delivery systems rely heavily on nanoparticles because they provide a targeted and monitored release of pharmaceuticals that maximize therapeutic efficacy and minimize side effects. To maximize drug internalization, this review focuses on comprehending the interactions between biological systems and nanoparticles. The way that nanoparticles behave during cellular uptake, distribution, and retention in the body is determined by their shape. Different forms, such as mesoporous silica nanoparticles, micelles, and nanorods, each have special properties that influence how well drugs are delivered to cells and internalized. To achieve the desired particle morphology, shape-controlled nanoparticle synthesis strategies take into account variables like pH, temperatures, and reaction time. Top-down techniques entail dissolving bulk materials to produce nanoparticles, whereas bottom-up techniques enable nanostructures to self-assemble. Comprehending the interactions at the bio-nano interface is essential to surmounting biological barriers and enhancing the therapeutic efficacy of nanotechnology in drug delivery systems. In general, drug internalization and distribution are greatly influenced by the shape of nanoparticles, which presents an opportunity for tailored and efficient treatment plans in a range of medical applications.

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.
CONCLUSIONS: Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Biogenic metallic nanoparticles (NPs) have garnered significant attention in recent years due to their unique properties and various applications in different fields. NPs, including gold, silver, zinc oxide, copper, titanium, and magnesium oxide NPs, have attracted considerable interest. Green synthesis approaches, utilizing natural products, offer advantages such as sustainability and environmental friendliness. The theranostics applications of these NPs hold immense significance in the fields of medicine and diagnostics. The review explores intricate cellular uptake pathways, internalization dynamics, reactive oxygen species generation, and ensuing inflammatory responses, shedding light on the intricate mechanisms governing their behaviour at a molecular level. Intriguingly, biogenic metallic NPs exhibit a wide array of applications in medicine, including but not limited to anti-inflammatory, anticancer, anti-diabetic, anti-plasmodial, antiviral properties and radical scavenging efficacy. Their potential in personalized medicine stands out, with a focus on tailoring treatments to individual patients based on these NPs\' unique attributes and targeted delivery capabilities. The article culminates in emphasizing the role of biogenic metallic NPs in shaping the landscape of personalized medicine. Harnessing their unique properties for tailored therapeutics, diagnostics and targeted interventions, these NPs pave the way for a paradigm shift in healthcare, promising enhanced efficacy and reduced adverse effects.

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 clathrin-mediated 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.
OBJECTIVE: 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.