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Measuring multisubunit mechanics of geometrically programmed colloidal assemblies via cryo-EM multi-body refinement
Programmable self-assembly has recently enabled the creation of complex structures through precise control of the interparticle interactions and the particle geometries. Targeting ever more structurally complex, dynamic, and functional assemblies necessitates going beyond the design of the structure itself, to the measurement and control of the local flexibility of the intersubunit connections and its impact on the collective mechanics of the entire assembly. In this study, we demonstrate a method to infer the mechanical properties of multisubunit assemblies using cryogenic electron microscopy (cryo-EM) and RELION’s multi-body refinement. Specifically, we analyze the fluctuations of pairs of DNA-origami subunits that self-assemble into tubules. By measuring the fluctuations of dimers using cryo-EM, we extract mechanical properties such as the bending modulus and interparticle spring constant. These properties are then applied to elastic models to predict assembly outcomes, which align well with experimental observations. This approach not only provides a deeper understanding of nanoparticle mechanics but also opens pathways to refining subunit designs to achieve precise assembly behavior. This methodology could have broader applications in the study of nanomaterials, including protein assemblies, where understanding the interplay of mechanical properties and subunit geometry is essential for controlling complex self-assembled structures.
Red cell distribution width (RDW) is independently associated with all-cause mortality in adult patients with osteomyelitis admitted to the intensive care unit
Objective This study aims to investigate the correlation between red cell distribution width (RDW) and overall mortality in adults diagnosed with osteomyelitis. Methods In this retrospective study, we examined data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, comprising 2,700 patients with osteomyelitis and available RDW data on the initial day of admission. Employing Kaplan-Meier survival analysis, we assessed the incidence rate of primary outcome events among groups categorized by RDW levels (Q1: RDW ≤ 13.5, Q2: 13.5 < RDW ≤ 14.6, Q3: 14.6 < RDW ≤ 16.1, Q4: 16.1 < RDW), with differences evaluated using the Log-rank test. Subsequently, Cox proportional hazards analyses were conducted to investigate the correlation between RDW and the overall mortality risk. Additionally, we performed stratified analyses based on factors such as gender, congestive heart failure, diabetes, and myocardial infarction to scrutinize the consistency of RDW’s prognostic significance. Results Over the 90-day follow-up, 10.7% of patients with osteomyelitis succumbed. Unadjusted RDW correlated significantly with in-hospital, 30-day, and 90-day mortality (p < 0.05). Higher RDW levels proved more effective in predicting increased risks. RDW emerged as an independent prognostic indicator, showing no significant interactions with sex, congestive heart failure, diabetes, and myocardial infarction (interaction p-values: 0.254 to 0.920). Conclusions The noteworthy link between RDW and heightened all-cause mortality in patients with osteomyelitis who were hospitalized in the intensive care unit highlights RDW’s potential as a valuable marker for identifying at-risk individuals during hospitalization.
Sorting nexin 3 promotes ischemic retinopathy through RIP1- and RIP3-mediated myeloid cell necroptosis and mitochondrial fission
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts. Myeloid cell-specific deficiency of Snx3 inhibited retinal neovascularization, hyperpermeability, and dysfunction in OIR mice. Using glutathione S-transferase pull-down, coimmunoprecipitation, and immunofluorescent staining, we found that SNX3 interacted with receptor-interacting protein 1/3 (RIP1 and RIP3). We further demonstrated that RIP1/3 degradation was accelerated in SNX3-deleted microglia/macrophages, causing an inhibition of hypoxia-induced necroptosis and mitochondrial fission, thereby decreasing the production of proinflammatory and proangiogenic factors (FGF2 and MMP12). Moreover, OIR retinas from myeloid cell–specific SNX3 overexpression transgenic mice presented more angiogenic tufts, while RIP1/3 inhibition largely ablated SNX3 overexpression–induced pathological angiogenesis. Based on the structure of SNX3, we identified a small-molecule inhibitor, W1122. Intriguingly, we found that W1122 effectively inhibited retinal angiogenesis in the OIR model, and combination treatment with anti-Vascular Endothelial Growth Factor (VEGF) yielded enhanced antiangiogenic effects. Collectively, our findings disclose a link between SNX3 and RIP1/3 signaling and implicate SNX3 in the development of ischemic retinopathy.
Effect of intermittent extracellular low-pH environment on human umbilical vein endothelial cell activity
Transcutaneous CO2 application promotes fracture healing and osteogenesis via angiogenesis. However, its molecular mechanism remains unclear. This therapy transiently decreases intra-tissue pH in the affected area to approximately 7.0 for 20 min, followed by recovery. We hypothesized that such intermittent pH changes activate endothelial cells similarly to acidic preconditioning. We aimed to investigate the response of human umbilical vein endothelial cells (HUVECs) to daily intermittent low-pH stimulation. HUVECs were cultured under three conditions: daily 20-min exposure to a low-pH medium (approximately 7.0), followed by a return to a control medium (approximately 7.4) (Change group); continuous exposure to a low-pH medium (Low pH group); constant culturing in a control medium (Control group). Cell proliferation, tube formation, migration, and protein/gene expression were assessed. Tube formation and migration were significantly enhanced in the Change group compared with those in the Control group, and tube formation was also increased in the Low pH group. Western blotting revealed upregulated expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in the Change group. CD31 gene expression was elevated in the Low pH and Change groups on Days 1 and 7, respectively. Phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (AKT) levels in the Low pH and Change groups were significantly increased compared with those in the Control, except for ERK2 in the Low pH group. The suppression of ERK1/2 or AKT by their inhibitors (U0126 and LY294002, respectively) during low-pH exposure inhibited proliferation and tube formation, indicating that the ERK1/2 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT pathways mediate endothelial cell activation in response to intermittent acidic stimulation. Intermittent low-pH exposure enhanced HUVEC activity, mediated by the ERK1/2 MAPK and PI3K/AKT pathways. Our findings provide insights into the mechanism by which transcutaneous CO2 application promotes angiogenesis and tissue repair.
Deep reinforcement learning control unlocks enhanced heat transfer in turbulent convection
Turbulent convection governs heat transport in both natural and industrial settings, yet optimizing it under extreme conditions remains a significant challenge. Traditional control strategies, such as predefined temperature modulation, struggle to achieve substantial enhancement. Here, we introduce a deep reinforcement learning (DRL) framework that autonomously discovers optimal control policies to maximize heat transfer in turbulent Rayleigh-Bénard convection. By dynamically adjusting wall temperature fluctuations, the DRL agent achieves a heat transfer enhancement of up to 38.5%, exceeding the 20 to 25% limit of conventional methods. The learned strategy reveals a nonlinear state–action relationship, inducing a fully modulated boundary layer regime. Furthermore, we distill the DRL insights into a simplified bang-bang control model, which retains comparable performance (up to 40.0% enhancement) and, crucially, generalizes to unseen, higher Rayleigh number cases without additional training. Our results demonstrate the power of machine learning in turbulence control and reveal a framework with potential for intelligent heat transfer optimization in real-world applications.
Experiences of adult children caring for parents aging in place
The rapid rise of the older adult population has increased the need for family caregiving. Adult children caring for their aging parents are exposed to a range of stressors, and their experiences shape care outcomes. We aim to describe these experiences using a grounded theory approach and develop a theory based on our findings. The inclusion criteria were adult children of any age who had provided care for at least one year to one or both parents, including parents-in-law, in a home setting. Participants were recruited using snowball sampling from community centers for older adults and churches. Espousing the grounded theory approach that often relies on interviews as a primary data collection method, 22 semi-structured personal interviews were conducted. Thematic analysis was completed using the NVivo software. The challenge-acceptance theory was developed through open coding, axial coding, selective coding, and continuous analysis of the data. The care recipients were aged 65 years and above. The caregivers’ experiences were summarized as a complex and dynamic process with negative and positive aspects, ranging from an increased level of stress and anxiety due to uncertainties of caregiving to the profound meaning and fulfillment experienced during the caregiving process. The results of the coding process consisted of four themes: the unknown, the need for effective communication, aging parents’ behavior, and caregiving. The resulting grounded theory, the challenge-acceptance theory, explains how caregivers transition from caregiving challenges to accepting the challenges. Caregivers struggle with caring for aging parents and experience severe stress, which may affect their health. Healthcare professionals should proactively identify and address these issues before significantly impacting caregivers’ health. Adequate communication with caregivers, provision of helpful resources, and promotion of proactive caregiving strategies can reduce caregiver burden and stress.
A genetically encoded nanobody sensor reveals conformational diversity in β-arrestins orchestrated by distinct seven transmembrane receptors
Agonist-induced interaction of G protein–coupled receptors (GPCRs) with β-arrestins (βarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor localization and signaling. While the underlying mechanism governing GPCR–βarr interaction is primarily conserved and involves receptor activation and phosphorylation, there are several examples of receptor-specific fine-tuning of βarr-mediated functional outcomes. Considering the key contribution of conformational plasticity of βarrs in driving receptor-specific functional responses, it is important to develop novel sensors capable of reporting distinct βarr conformations in cellular context. Here, we design an intrabody version of a βarr-recognizing nanobody (nanobody32), referred to as intrabody32 (Ib32), in NanoLuc enzyme complementation assay format and measure its ability to recognize βarr1 and 2 in live cells upon activation of a broad set of GPCRs. Ib32 robustly recognizes activated βarr1 and 2 in the plasma membrane and endosomes, and effectively mirrors βarr recruitment profile upon stimulation of selected GPCRs. We also design an Ib32 sensor for polarization microscopy with a change in linear dichroism as readout and demonstrate its utility for monitoring βarr activation upon stimulation of selected GPCRs by natural and biased agonists. Taken together with a previously described sensor of βarr1 activation, Ib32 underscores the inherent flexibility encoded in βarrs and conformational diversity imparted by different GPCRs, which is further corroborated using an orthogonal limited proteolysis assay. Our study presents Ib32 as a sensor of βarr activation and highlights the structural diversity of βarrs, which likely allows their ability to interact with, and regulate, a large repertoire of GPCRs.
Challenges and perceptions of dental undergraduate students regarding active learning in clinical practice: A qualitative study
Objectives This study aimed to investigate the challenges faced by dental students during clinical practice and to understand their perceptions of how active learning methodologies contribute to fostering critical and reflective participation in problem-solving throughout the teaching-learning process. Methods This qualitative study applied the action research method in a descriptive and interpretive manner, implementing active learning methodologies in the adolescent clinic of the Federal University of Uberlândia (Brazil). This clinic is among the fundamental elements in the Public Health System. This research included 33 students in the final term of the dentistry course (10th term), divided into three groups of 9–13 students each, and regularly enrolled in clinic practice. The data was collected in three 90-minute workshops with each group. This study used Minayo’s methodological framework and the arc method by Spanish educator Charles Maguerez to conduct the action research. This research comprised five steps: 1. Clinical experience; 2. Identification of challenges; 3. Theorization of challenges based on scientific evidence; 4. Development of action strategies; 5. Application of strategies in clinical practice. The theoretical framework was Paulo Freire’s problematization methodology. Data analysis followed the thematic content analysis technique. Results After comprehensive data analysis, the main challenges concerned the work process, productivity, and infrastructure. The formulated strategies included the establishment of a procedures table, implementation of minimum age regulations for companions in the waiting area, adjustment of clinic hours, enhancement of auxiliary professional training, and maintenance of dental equipment. Conclusion The groups’ experience with active methods qualified them to identify and address relevant practice challenges. It allowed study participants to lead their teaching-learning process and develop action strategies to transform the work process. Reflecting on implementing these strategies in clinical practice transformed the students’ reality and promoted more dynamic and meaningful learning. However, solving challenges, such as infrastructure, requires a continuous commitment of financial resources and institutional support.
Convergent evolution of <i>NFP</i> -facilitated root nodule symbiosis
The origin and phylogenetic distribution of symbiotic associations between nodulating angiosperms and nitrogen-fixing bacteria have long intrigued biologists. Recent comparative evolutionary analyses have yielded alternative hypotheses: a multistep pathway of independent gains and losses of root nodule symbiosis vs. a single gain followed by numerous losses. A detailed reconstruction of the history of genes involved in signaling between nitrogen-fixing bacteria and potential hosts, particularly lipo-chitooligosaccharide (LCO) signaling, is needed to distinguish between these hypotheses. LCO recognition by plants involves the Nod Factor Perception ( NFP ) gene family; in the legume model Medicago truncatula (Fabales), MtNFP is essential for establishing rhizobial symbiosis. Here, we document convergent evolution of NFP , indicating multiple origins of LCO-driven symbiosis. In contrast to previous models that explain the recruitment of NFP via a single duplication in the ancestor of the nitrogen-fixing clade, our phylogenomic and synteny results suggest this duplication does not span the entire clade. Tandem duplication in a common ancestor of Cucurbitales and Rosales resulted in the NFP1 and NFP2 groups. In contrast, the phylogenetically closest paralog of MtNFP is MtLYR1 , located on a different chromosome within a large syntenic block. All available data indicate that a large-scale duplication resulted in MtNFP and MtLYR1 , likely corresponding to a whole-genome duplication in an ancestor of subfamily Papilionoideae of Fabaceae. We show that MtNFP and the NFP2 -like group are not orthologous, indicating multiple independent gains of NFP -based LCO signaling. This molecular convergence provides a possible mechanism for multiple gains of root nodule symbiosis across the nitrogen-fixing clade.
Implicit benefits of adolescents with high psychological resilience in action control of emotion regulation
Psychological resilience is crucial for adolescents’ emotional health. The aim of this study was to evaluate the relationship between psychological resilience and implicit emotion regulation. The action control theory was used as a model reference. Experiment 1 employed an emotion regulation-implicit associations task using a sample of 56 adolescents and was designed to compare implicit attitudes toward emotion regulation between individuals with high and those with low psychological resilience. The results reveal that adolescents with high psychological resilience are more inclined to use controlled emotion regulation to regulate their emotions. Experiment 2 was an indirect examination of the differences between the implicit emotion repair effects of adolescents with high and those with low psychological resilience (n = 75). The findings indicate that adolescents with high (vs. low) psychological resilience search faster to detect happy faces in an angry context. The results of the two experiments consistently suggest that adolescents with high psychological resilience have an implicit advantage in emotion regulation, which contributes to their emotional health.
Stress-induced organismal death is genetically regulated by the mTOR–Zeste–Phae1 axis
All organisms are exposed to various stressors, which can sometimes lead to organismal death, depending on their intensity. While stress-induced organismal death has been observed in many species, the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms of stress-induced organismal death in the fruit fly Drosophila melanogaster . We identified a chymotrypsin-like serine protease Phaedra1 ( Phae1 ) as a death mediator in D. melanogaster larvae. Phae1 expression was up-regulated by lethal heat stress (40 °C) but not nonlethal heat stress (38 °C or lower). The most prominent induction of Phae1 occurred in the central nervous system (CNS). We found neuro-specific knockdown of Phae1 increased survival and reduced neuronal caspase activity following exposure to lethal heat stress, suggesting that the transcriptional upregulation of Phae1 in the CNS is essential for stress-induced organismal death. We next found via bioinformatic and biochemical analyses that the transcription factor Zeste (Z) bound the Phae1 enhancer region and that z loss-of-function impaired Phae1 induction in the CNS, increasing survival following lethal heat stress. In addition, we found via chemical screening that rapamycin, a chemical inhibitor of mechanistic target of rapamycin (mTOR), suppressed Phae1 expression. Neuro-specific knockdown of mTor reduced the protein levels of both Phae1 and Z, leading to an increase in survival following lethal heat stress. Together, these results indicate that heat stress–induced organismal death in D. melanogaster larvae is regulated by a genetically encoded transcriptional signaling pathway involving the mTOR–Z–Phae1 axis.
Statins to reduce renal sinus fat among breast cancer patients undergoing anthracycline-based chemotherapy: A substudy of PREVENT-WF-98213
Objective To test if statin administration attenuated renal sinus fat (RSF) accumulation and if RSF was associated with renal function in women with breast cancer (BC) receiving anthracycline-based chemotherapy. Methods This was a secondary analysis in a subgroup of women with stage I-III BC randomized to placebo (n = 35) or statin (40 mg/day atorvastatin, n = 44) therapy. At baseline and 24-months after randomization, RSF and intraabdominal fat were measured from magnetic resonance images, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Results Participants in this study averaged 51 years of age (SD 11), 87% reported White race, and had a mean BMI (±SD) of 30.2 kg/m2 (±6.1). Most participants (60%) were diagnosed with stage II BC. At 24-months, RSF was higher in the placebo group relative to the statin group (β [95% CI], p-value: 0.17 [0.009, 0.34], p = 0.04). After adjusting for baseline RSF, this signal remained but was attenuated (β [95% CI], p-value: 0.12 [−0.06, 0.29], p = 0.18). In all participants at baseline and prior to beginning chemotherapy for BC or study drug, higher RSF was associated with lower eGFR values in all participants (r = −0.23, p = 0.03). At 24-months by study group, greater RSF was associated with decreased eGFR in the placebo group (−0.51, p = 0.01) but not in the statin group (−0.25, p = 0.19). Discussion Statin administration may lower RSF during anthracycline-based chemotherapy. These findings merit further investigation to determine if statins protect renal function during BC treatment.
Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis
MS4A4A belongs to the MS4A tetraspan protein superfamily and is selectively expressed by the monocyte–macrophage lineage. In this study, we aimed to evaluate the role of MS4A4A+ macrophages in rheumatoid arthritis (RA) pathogenesis and response to treatment. RNA sequencing and immunohistochemistry of synovial samples from either early treatment-naïve or active chronic RA patients showed that MS4A4A expression positively correlated with synovial inflammation. Synovial macrophages from patients treated with corticosteroids (CS) exhibited an enhanced expression of MS4A4A and Fc γ receptor (FcγR) 3. Accordingly, CS enhanced in vitro the expression of MS4A4A and FcγR3 in human and murine macrophages. In an experimental model of arthritis, Ms4a4a deletion had no effect on the disease course but was associated with enhanced therapeutic response selectively to CS. These results suggest that macrophage expression of MS4A4A represents a biomarker of joint inflammation in RA and that its upregulation in concert with FcγR3 by CS counteracts the therapeutic activity of these drugs. Macrophage MS4A4A may represent a biomarker of joint inflammation in RA and a target to amplify the therapeutic activity of CS.
A deep learning approach to gender equality: Forecasting educational indicators with 1D-CNN aligned with SDG 5
Sustainable development goal (SDG) 5 focuses on gender equality and empowerment and it is considered as one of the most important SDGs. Therefore, this article presented a time series prediction model that predicts gender-related educational results in the US, Saudi Arabia, China, Egypt, and Sweden. By analyzing gender-disaggregated demographic, socioeconomic, and educational data, the 1 DCNN can reveal temporal patterns and discrepancies. The main reason for selecting 1D-CNN as a deep learning model is its ability to model sequential data and detect minor changes. Through implementing the 1 DCNN with verified historical data, realistic progress trajectories have been predicted, which are suited to the particular circumstances of each country. The results obtained from the proposed model show that the model can produce important predictions in a range of gender-focused educational measures. In addition, it provides useful information that helps organizations develop, educators, politicians, and gender activists. In Conclusion, the results presented in this paper improve evidence-based planning and focused interventions, which hasten the advancement of gender equity in education and other fields.
Giant mobility of surface-trapped ionic charges following liquid tribocharging
The sliding motion of aqueous droplets on hydrophobic surfaces leads to charge separation at the trailing edge, with implications from triple-line friction to hydrovoltaic energy generation. Charges deposited on the solid surface have been attributed to ions or electrons ripped off from the liquid drop. However, the dynamics and exact physicochemical nature of these surface-trapped charges remains poorly explored. Here, we take advantage of a scanning-based electrostatic mapping technique, to directly quantify the spatiotemporal dynamics of surface deposited charges in the wake of droplets sliding on hydrophobic surfaces. We confirm the ionic nature of these interfacially trapped charges, and evidence that they undergo very fast bidimensional diffusive transport, gliding with low friction at the solid/gas interface. We interpret our observations in the framework of molecular dynamics simulation of hydrated ions adsorbed on solid surfaces, revealing a peculiar transport mechanism limited by purely interfacial friction of the ionic solvation shell with the solid surface. By uncovering the unexpected dynamics of these ionic puddles—a distinct state of interfacial ionic matter—our findings have general implications for molecular-scale ionic transport, electrified matter, and wetting dynamics at interfaces.
Investigation of bacterial community and histamine production in fresh mackerel at low temperature storage
This study investigates microbial growth, community composition, and histamine production in freshly caught mackerel stored at 4°C and 10°C. Fish were obtained directly from fishermen and immediately placed in low-temperature storage to minimize external contamination. Microbial activity was assessed using total viable count, amplicon sequencing, and HPLC analysis. The total bacterial count exceeded 5 log CFU/mL after 5 days at 4°C and 2 days at 10°C, indicating the presence of histamine-producing bacteria (HPB), particularly under psychrophilic conditions. Photobacterium was identified as the dominant bacterial genus at both temperatures, suggesting its role as a key psychrophilic HPB. Histamine levels increased progressively, reaching 5.11 ± 2.43 ppm at 4°C and 11.18 ± 4.67 ppm at 10°C, while histidine content declined. Despite cold storage and strict contamination control, naturally occurring bacteria in fish continued to grow and produce histamine. These findings highlight the importance of temperature control in preventing histamine accumulation and provide new insights into microbial dynamics and food safety risks in fresh mackerel.
S-nitrosylation of pVHL regulates β <sub>2</sub> adrenergic receptor function
The β 2 -adrenergic receptor (β 2 AR), a prototype G protein–coupled receptor, controls cardiopulmonary function underpinning O 2 delivery. Abundance of the β 2 AR is canonically regulated by G protein–coupled receptor kinases and β-arrestins, but neither controls constitutive receptor levels, which are dependent on ambient O 2 . Basal β 2 AR expression is instead regulated by the prolyl hydroxylase/pVHL-E3 ubiquitin ligase system, explaining O 2 responsivity. Interplay between O 2 and nitric oxide (NO, a potent bronchodilator) is central to cardiopulmonary function. Here, we demonstrate that pVHL-mediated β 2 AR degradation is counteracted by NO, revealing pVHL control of pulmonary function. NO S-nitrosylates Cys77 in human pVHL (cognate to mouse Cys43), which induces binding of the E3 ubiquitin ligase c-Cbl to degrade pVHL, thereby increasing β 2 AR expression. pVHL–C43S mutant mice refractory to S-nitrosylation exhibit decreases in β 2 AR signaling and increases in airway tone. Thus, pVHL controls adrenergic pulmonary function and contributes to bronchodilation by NO. Our findings suggest therapeutic approaches to asthma and obstructive airway disease.
Physical activity levels, exercise intrinsic motivation, physical fitness, and their association with adiposity and Oxytocin Receptor (OXTR) rs53576 and rs2254298 gene variants
Intrinsic motivation predicts higher exercise participation and long-term sustenance. Common variants in the oxytocin receptor gene (OXTR) have been associated with socially-related personality traits and behaviours, and obesity pathogenesis. The study aims to investigate the association of physical activity (PA) level, intrinsic motivation, and physical fitness, with adiposity and OXTR rs53576 and rs2254298 among a sample of Malaysian urban young adults in Sunway University. A total of 273 participants (M/F = 118/155; aged 21.5 ± 2.9) self-reported their socio-demographics, PA levels via International Physical Activity Questionnaire (IPAQ) Short Form, and intrinsic motivation via Motives for Physical Activities Measure – Revised (MPAM-R). Physical fitness was assessed by three-minute step test, while anthropometric and body composition measurements were taken. Genotyping was performed by allele-specific real-time PCR. Men reported higher PA levels and higher Interest, Competence, and Social scores than women. Interest and Competence scores were significantly positively correlated with vigorous, moderate and total METs, and were also significantly associated with Waist-Height Ratio. Fitness was significantly associated with Waist-Hip Ratio. Physical fitness was significantly positively correlated with vigorous and total METs. OXTR rs53576 was significantly associated with Appearance only, but not PA levels, physical fitness, and adiposity. Men were more physically active and intrinsically more motivated to exercise than women. The desire to have fun and engage with challenges when exercising correlates with more frequent exercise, and is a predictor of lower adiposity. OXTR rs53576 influences motivation for being physically active in order to become more physically attractive.
Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion. The hybrid-cell-derived exosomes could combine the functional properties of both parental cells and be readily produced by passaging. This method enables customization and large-scale production of exosomes with specific functionalities, potentially advancing precision therapies across a wide array of diseases. As demonstrated in Alzheimer’s disease (AD) models, exosomes derived from hybrid cells (HCs) (H/Exos) of mesenchymal stem cells (MSCs) and neutrophils efficiently targeted AD-affected areas via LFA-1/ICAM-1 and improved the cognition of AD mice. Beyond directly promoting neural repair and inhibiting inflammation, we surprisingly found that H/Exos increased microglia abundance, modulated microglia gene expression, enhanced the endocytic and lysosomal function, and promoted microglial phagocytic phenotypic differentiation to clear Aβ. This hybridoma-inspired strategy offers a versatile and practical way to engineer exosomes with desired therapeutic functions, representing a promising direction for personalized therapies.
Establishing a new rat model to investigate pathophysiology and bone healing in posttraumatic lymphedema
Introduction Posttraumatic lymphedema is a common complication after open and closed fractures with soft tissue trauma. Even though there is quite certain consensus about the basic mechanisms of lymphedema formation, the pathophysiology on a cellular and molecular base is largely unknown. Furthermore, there is currently no data on the interaction of lymphedema and bone regeneration. Subsequently, the aim of this study was to establish an animal model specific to posttraumatic lymphedema, which can be used to conduct future investigations into the pathophysiology and bone regeneration in lymphedema. Methods The test animals (rats)In wild-type Fisher 344 rats were divided into three groups: group one had an isolated bone defect, group two had an isolated soft tissue defect, and group three had a combination of bone and soft tissue trauma. Results Using volumetric and circumferential measurements, a significant increase in circumference and volume in the sense of lymphedema could be detected, particularly 3–4 weeks after trauma in the groups with soft tissue trauma, whereas the creation of a bony defect did not appear to have a significant influence on the swelling. Microscopic images of the lymphatic drainage pathways verified the lymphatic drainage disorder weeks after soft tissue trauma. Conclusion Consequently, the established model can be used to investigate the exact pathophysiology of post-traumatic lymphedema. Furthermore, it seems to be suitable as a model for investigating bone regeneration in manifest lymphedema.