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MOTS-c mimics exercise to combat diabetic liver fibrosis by targeting Keap1-Nrf2-Smad2/3
Memristive Bellman solver for decision-making
From home to the screen: How parental rejection fuels cyberbullying in college students
Previous research has highlighted the impact of family environment on college students’ cyberbullying behavior, yet the role of parenting styles, particularly negative ones, remains underexplored. This study, grounded in the interpersonal acceptance-rejection theory and social information processing model, investigates how parental rejection influences cyberbullying behavior among college students through cognitive and emotional mechanisms. We surveyed 1,567 college students (620 males, 947 females; average age: 19.34 ± 1.24 years) from several universities in Shandong and Jilin provinces, China. Participants completed questionnaires assessing cyberbullying, parental rejection, empathy, and moral disengagement. The findings reveal that 456 individuals (29.1%) had engaged in at least one instance of cyberbullying behavior, including 180 males and 276 females. Subsequently, an investigation into the cyberbullying behaviors of these individuals revealed that: (1) parental rejection is a significant predictor of cyberbullying behavior; (2) empathy and moral disengagement serve as partial mediators in the relationship between parental rejection and cyberbullying; (3) both empathy and moral disengagement act as sequential mediators in this relationship. These results underscore the importance of empathy and moral disengagement in understanding the link between parental rejection and cyberbullying among college students, offering a new theoretical perspective for future interventions.
Investigation of heat transfer performance in heat exchangers using hybrid nanofluids and twisted tape inserts with fixed special rings
Clustering of NLRP3 induced by membrane or protein scaffolds promotes inflammasome assembly
Abstract NLRP3 is a pattern recognition receptor forming an inflammasome in response to diverse pathogen and self-derived triggers, but molecular insights on NLRP3 activation are still lacking. Here, we drive ectopic NLRP3 to different subcellular locations in NLRP3-deficient macrophages to map the spatial activation profile of NLRP3, and find that NLRP3 variants enriched at the organellar membranes respond to canonical triggers similarly to wild-type NLRP3; however, unlike wild-type, these NLRP3 variants can be activated even in the absence of the polybasic phospholipid-binding segment. Mechanistically, membrane or protein scaffolds mediate NLRP3 clustering, which leads to the unfastening of the inactive NACHT domain conformation preceding the activated NLRP3 oligomer formation. Our data thus suggest that scaffold-promoted clustering is an important step in NLRP3 activation, enabling NLRP3 to sense distinct activator-induced cellular anomalies exhibited via lipid or protein assemblies, thereby establishing NLRP3 as the master sensor of perturbations in cell homeostasis.
Expression, purification and preliminary pharmacological characterization of the Plasmodium falciparum membrane-bound pyrophosphatase type 1
Membrane-bound pyrophosphatases are integral membrane proteins that catalyze the hydrolysis of pyrophosphate into orthophosphate, while simultaneously facilitating the pumping of protons and/or sodium ions. Since mPPases are absent in humans but play a critical role in the life cycle of protist parasite, they represent promising therapeutic targets. We successfully expressed the Plasmodium falciparum type 1 mPPase in the baculovirus/insect cell expression system and purified the protein, yielding 0.3 mg per liter cell culture. Various detergents were tested for solubilization, with the protein remaining active under all selected detergents. n -dodecyl-β-D-maltoside combined with cholesteryl hemisuccinate provided the highest solubility (88%). Finally, the PfPPase-VP1 was assayed against a set of fourteen antimalarial drugs, along with seven Thermotoga maritima mPPase inhibitors and fourteen compounds of unknown activity against mPPases. Only three compounds, all pyrazolo[1,5- a ]pyrimidine-based TmPPase inhibitors, retained micromolar IC 50 activity against PfPPase-VP1. The expression and purification of the PfPPase-VP1 will allow to conduct structural studies as well as to develop target-based screens, two steps necessary for the development of inhibitors to combat parasite disease.
Plasma inflammation-related proteins associated with anxiety and depression disorders in IBD patients
Elastocapillary sequential fluid capture in hummingbird-inspired grooved sheets
Abstract Passive and effective fluid capture and transport at small scale is crucial for industrial and medical applications, especially for the realisation of point-of-care tests. Performing these tests involves several steps, including capturing biological fluid, aliquoting, reacting with reagents, and reading the results. Ideally, these tests must be fast and offer a large surface-to-volume ratio to achieve rapid and precise diagnostics with a reduced amount of fluid. Such constraints are often contradictory as a high surface-to-volume ratio implies a high hydraulic resistance and hence a decrease in the flow rate. Inspired by the feeding mechanism of hummingbirds, we propose a frugal fluid capture device that takes advantage of elastocapillary deformations to enable concomitant fast liquid transport, aliquoting, and high confinement in the deformed state. The hierarchical design of the device – that consists in vertical grooves stacked on an elastic sheet – enables a two-step sequential fluid capture. Each unit groove mimics the hummingbird’s tongue and closes due to capillary forces when a wetting liquid penetrates, yielding the closure of the whole device in a tubular shape, in the core of which additional liquid is captured. Combining elasticity, capillarity, and viscous flow, we rationalise the fluid-structure interaction at play both when liquid is scarce and abundant. By functionalising the surface of the grooves, such a passive device can concomitantly achieve all the steps of point-of-care tests, opening the way for the design of optimal devices for fluid capture and transport in microfluidics.
Application of a grey wolf optimization-enhanced convolutional neural network and bidirectional gated recurrent unit model for credit scoring prediction
With the digital transformation of the financial industry, credit score prediction, as a key component of risk management, faces increasingly complex challenges. Traditional credit scoring methods often have difficulty in fully capturing the characteristics of large-scale, high-dimensional financial data, resulting in limited prediction performance. To address these issues, this paper proposes a credit score prediction model that combines CNNs and BiGRUs, and uses the GWO algorithm for hyperparameter tuning. CNN performs well in feature extraction and can effectively capture patterns in customer historical behaviors, while BiGRU is good at handling time dependencies, which further improves the prediction accuracy of the model. The GWO algorithm is introduced to further improve the overall performance of the model by optimizing key parameters. Experimental results show that the CNN-BiGRU-GWO model proposed in this paper performs well on multiple public credit score datasets, significantly improving the accuracy and efficiency of prediction. On the LendingClub loan dataset, the MAE of this model is 15.63, MAPE is 4.65%, RMSE is 3.34, and MSE is 12.01, which are 64.5%, 68.0%, 21.4%, and 52.5% lower than the traditional method plawiak of 44.07, 14.51%, 4.25, and 25.29, respectively. In addition, compared with traditional methods, this model also shows stronger advantages in adaptability and generalization ability. By integrating advanced technologies, this model not only provides an innovative technical solution for credit score prediction, but also provides valuable insights into the application of deep learning in the financial field, making up for the shortcomings of existing methods and demonstrating its potential for wide application in financial risk management.
Preparation and characterization of biodegradable flexible polyurethane foam containing acetylated tapioca starch and Castor oil
Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function
The instability mechanisms and precursor information of different type rocks based on acoustic emission
This study presented the results of indoor uniaxial compression and acoustic emission (AE) monitoring tests for five type rocks: marble, granite, siltstone, sandstone and limestone. The experiment adopted a displacement-controlled loading method with a loading rate of 0.18mm/min, and AE monitoring was carried out synchronously. Some AE parameters were obtained. Detailed analysis of AE parameters RA and AF values revealed the evolutionary laws of the RA/AF value distribution range and rock failure mechanisms for five different type rocks; The models of damage types inside rocks over time had been established. Furthermore, the microseismic parameter lgN/b was introduced. Analyzing the lgN/b values dynamic change process revealed the instability laws, and rock instability precursor information was obtained. The results showed that an increase in the proportion of shear cracks, along with a wider range of the RA/AF values distribution can serve as precursor information for rock instability. Before rock failure occurred, the lgN/b values consistently increased. Additionally, the study found that the change laws of lgN/b values can reveal the extent of development of intrinsic weak structures inside the rocks. Through a multi-parameter and multi-method comprehensive analysis, we can more scientifically identify the instability precursor information of different type rocks in terms of time, and the hierarchical warning was achieved. The research results can provide a reference for microseismic monitoring at various sites and establish certain scientific basis for effective on-site warning strategies.
Characterizing the childhood roots of adult sense of mastery across 22 countries in the global flourishing study
Abstract How might we cultivate a life imbued with a sense of mastery? An expanding body of research demonstrates that a heightened sense of mastery improves health and well-being outcomes. Despite this, it remains unclear which childhood factors foster increased mastery in adulthood. Further, existing studies have examined this question only within single countries. We analyzed nationally representative data from 22 countries in the Global Flourishing Study (N = 202,898) and evaluated if 11 aspects of a child’s upbringing predict mastery in adulthood, and also whether these associations vary by country. Some childhood factors were associated with increased mastery in adulthood, including good health, good relationships with mothers and fathers, economic stability, and regular religious service attendance. Childhood factors associated with decreased mastery in adulthood included abuse, feeling like an outsider in one’s family, poor health, economic hardship, and being female. However, there was little evidence that parent marital status or immigration status in childhood were associated with mastery in adulthood. Our meta-analysis also revealed substantial heterogeneity in childhood pathways to adult mastery across 22 countries. With further research, these findings could inform the development of globally adaptable, yet locally nuanced, programs and policies designed to foster a mastery across the globe.
Flamingos use their L-shaped beak and morphing feet to induce vortical traps for prey capture
Flamingos feature one of the most sophisticated filter-feeding systems among birds, characterized by upside-down feeding, comb-like lamellae, and a piston-like tongue. However, the hydrodynamic functions of their L-shaped chattering beak, S-curved neck, and distinct behaviors such as stomping and feeding against the flow remain a mystery. Combining live flamingo experiments with live brine shrimp and passive particles, bioinspired physical models, and 3D CFD simulations, we show that flamingos generate self-induced vortical traps using their heads, beaks, and feet to capture agile planktonic prey in harsh fluid environments. When retracting their heads rapidly (~40 cm/s), flamingos generate tornado-like vortices that stir up and upwell bottom sediments and live shrimp aided by their L-shaped beak. Remarkably, they also induce directional flows (~7 cm/s) through asymmetric beak chattering underwater (~12 Hz). Their morphing feet create horizontal eddies during stomping, lifting, and concentrating sediments and brine shrimp, while trapping fast-swimming invertebrates, as confirmed by using a 3D-printed morphing foot model. During interfacial skimming, flamingos produce a vortical recirculation zone at the beak’s tip, aiding in prey capture. Experiments using a flamingo-inspired particle collection system indicate that beak chattering improves capture rates by ~7×. These findings offer design principles for bioinspired particle collection systems that may be applied to remove pollutants and harmful microorganisms from water bodies.
Economic and sustainable revolution to facilitate one-carbon biomanufacturing
The global health burden of pediatric chronic kidney disease: An analysis of the Global Burden of Disease database from 1990 to 2021
Background Chronic kidney disease (CKD) poses a significant global health challenge; however, its burden on pediatric populations remains underexplored. This study assesses the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of pediatric CKD attributable to type 1 diabetes mellitus, type 2 diabetes mellitus, hypertension, glomerulonephritis, and congenital anomalies of the kidney and urinary tract from 1990 to 2021. Methods Data were extracted from the Global Burden of Disease (GBD) 2021 database. CKD burden was stratified by etiology, age, sex, sociodemographic index (SDI), and geography. Average annual percentage changes (AAPCs) in incidence, prevalence, mortality, and DALYs were calculated. Results Globally, CKD-related mortality and DALYs decreased for type 1 diabetes mellitus (-2.176% AAPC), type 2 diabetes mellitus (-1.556%), glomerulonephritis (-0.854%), hypertension (-0.800%), and congenital anomalies of the kidney and urinary tract (-2.143%). The incidence of hypertension incidence increased (+1.299%). Boys experienced higher incidence and prevalence rates for all etiologies, while girls had more significant reductions in mortality and DALYs. High-SDI regions showed the steepest declines in CKD burden, while low-SDI regions experienced limited reductions and increasing hypertension prevalence. Conclusions Pediatric CKD burden reflects disparities by etiology, geography, and SDI. Interventions to improve early diagnosis, healthcare access, and targeted management strategies, particularly in low-SDI regions, are essential. Addressing obesity and improving treatment for glomerulonephritis are priorities. Standardized diagnostic criteria and broader global efforts are needed to mitigate the burden of pediatric CKD.
The comparison of two types of physiotherapy techniques on selected weaning indices of patients requiring mechanical ventilation: a single blind randomized controlled trial
Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells
Abstract Targeted kinase inhibitors are a cornerstone of cancer therapy, but their success is often hindered by the complexity of cellular signaling networks that can lead to resistance. Overcoming this challenge necessitates a deep understanding of cellular signaling responses. While standard global phosphoproteomics offers extensive insights, lengthy processing times, the complexity of data interpretation, and frequent omission of crucial phosphorylation sites limit its utility. Here, we combine data-independent acquisition (DIA) with spike-in of synthetic heavy stable isotope-labeled phosphopeptides to facilitate the targeted detection of particularly informative phosphorylation sites. Our spike-in enhanced detection in DIA (SPIED-DIA) approach integrates the improved sensitivity of spike-in-based targeted detection with the discovery potential of global phosphoproteomics into a simple workflow. We employed this method to investigate synergistic signaling responses in colorectal cancer cell lines following MEK inhibition. Our findings highlight that combining MEK inhibition with growth factor stimulation synergistically activates JNK signaling in HCT116 cells. This synergy emphasizes the therapeutic potential of concurrently targeting MEK and JNK pathways, as evidenced by the significantly impaired growth of HCT116 cells when treated with both inhibitors. Our results demonstrate that SPIED-DIA effectively identifies synergistic signaling responses in colorectal cancer cells, presenting a valuable tool for uncovering new therapeutic targets and strategies in cancer treatment.
NR2F6 promotes the malignant progression of neuroblastoma as an indicator of poor prognosis
Background NR2F6 is an orphan nuclear receptor with dual tumorigenic activity in the immune system and tumor cells, playing an essential role in tumor differentiation and immunity. This study aimed to investigate the expression level of NR2F6 in various tumors and its effect on neuroblastoma (NB). Methods We evaluated the role of NR2F6 in the genesis and development of 34 different tumors through multiple databases. In addition, we investigated the effects of NR2F6 expression levels on NB risk factors and prognosis using pathology sections and clinical data from primary retroperitoneal NB in children. The effects on cell proliferation, invasion, and migration were explored by knocking down NR2F6 expression in SK-N-BE(2) and SK-N-SH cells. Results The findings showed that NR2F6 was significantly correlated with the prognosis of NB and was an important indicator suggesting disease regression. In addition, NR2F6 knockdown slowed down NB cells’ proliferation, invasion, and migration ability in vitro. Conclusion Our results suggest that NR2F6 plays a crucial role in tumor-promoting effects and can be used as a potential prognostic marker for NB.