Browse Articles

Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles

Abstract Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts. The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona, which varies patient-to-patient and as a function of disease state. This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions, phenotypes, and cytokine responses. NP coronas alter cell associations in a disease-dependent manner, induce differential co-stimulatory and co-inhibitory molecule expression, and influence cytokine release. Integrated multi-omics analysis of proteomics, lipidomics, metabolomics, and cytokine datasets highlight a set of differentially enriched TLR4 ligands that correlate with dynamic NP corona-mediated immune activation. Pharmacological inhibition and genetic knockout studies validate that NP coronas mediate this response through TLR4/MyD88/NF-κB signaling. Our findings illuminate the personalized nature of corona formation under a dynamic inflammatory condition and its impact on NP-mediated immune activation profiles and inflammation, suggesting that disease progression-related alterations in plasma composition can manifest in the corona to cause unintended toxicity and altered therapeutic efficacy.

Modeling of lifetime scenarios with non-monotonic failure rates

The Weibull distribution is an important continuous distribution that is cardinal in reliability analysis and lifetime modeling. On the other hand, it has several limitations for practical applications, such as modeling lifetime scenarios with non-monotonic failure rates. However, accurate modeling of non-monotonic failure rates is essential for achieving more accurate predictions, better risk management, and informed decision-making in various domains where reliability and longevity are critical factors. For this reason, we introduce a new three parameter lifetime distribution—the Modified Kies Weibull distribution (MKWD)—that is able to model lifetime scenarios with non-monotonic failure rates. We analyze the statistical features of the MKWD, such as the quantile function, median, moments, mean, variance, skewness, kurtosis, coefficient of variation, index of dispersion, moment generating function, incomplete moments, conditional moments, Bonferroni, Lorenz, and Zenga curves, and order statistics. Various measures of uncertainty for the MKWD such as Rényi entropy, exponential entropy, Havrda and Charvat entropy, Arimoto entropy, Tsallis entropy, extropy, weighted extropy and residual extropy are computed. We discuss eight different parameter estimation methods and conduct a Monte Carlo simulation study to evaluate the performance of these different estimators. The simulation results show that the maximum likelihood method leads to the best results. The effectiveness of the newly suggested model is demonstrated through the examination of two different sets of real data. Regression analysis utilizing survival times data demonstrates that the MKWD model offers a superior match compared to other current distributions and regression models.

Application of Perclose ProGlide closure device in transbrachial endovascular intervention

Enantioselective Heck/Tsuji−Trost reaction of flexible vinylic halides with 1,3-dienes

Abstract The enantioselective domino Heck/cross-coupling has emerged as a powerful tool in modern chemical synthesis for decades. Despite significant progress in relative rigid skeleton substrates, the implementation of asymmetric Heck/cross-coupling cascades of highly flexible haloalkene substrates remains a challenging and and long-standing goal. Here we report an efficient asymmetric domino Heck/Tsuji−Trost reaction of highly flexible vinylic halides with 1,3-dienes enabled by palladium catalysis. Specifically, the Heck insertion as stereodetermining step to form ƞ 3 allyl palladium complex and in situ trapping with nucleophiles enable efficient Heck/etherification in a formal (4 + 2) cycloaddition manner. Engineering the Sadphos bearing androgynous non-C 2 -symmetric chiral sulfinamide phosphine ligands are vital component in achieving excellent catalytic reactivity and enantioselectivity. This strategy offers a general, modular and divergent platform for rapidly upgrading feedstock flexible vinylic halides and dienes to various value-added molecules and is expected to inspire the development of other challenging enantioselective domino Heck/cross-couplings.

Parental divorce’s long shadow: Elevated stroke risk among older Americans

Although studies have investigated the association between adverse childhood experiences and chronic health outcomes including stroke, few studies have investigated the association between parental divorce and stroke among adults with no history of childhood abuse. The objectives of this study were to investigate the association between parental divorce in childhood and stroke in older adulthood among those who did not experience child abuse and to examine whether this association differs between men and women. This study utilized population-based data from the 2022 Behavioral Risk Factor Surveillance System. An analytic sample of 13,205 adults aged 65 and above (56.6% female) who have never experienced childhood physical nor sexual abuse were analyzed using binary logistic regression. The outcome variable investigated was self-report of a physician-diagnosis of stroke, and the main exposure of interest was parental divorce. In this sample of older adults, 7.3% reported having stroke, while 13.9% reported that their parents had divorced before the respondent was 18 years old. Controlling for the effects of other factors, respondents who experienced parental divorce had 1.61 times higher odds of having a stroke when compared to their counterparts who did not experience parental divorce (AOR = 1.61, 95% CI = 1.15–2.24). The association between parental divorce and stroke was not dependent on sex; however, compared to females, males had 1.47 times higher odds of having a stroke (AOR = 1.47, 95% CI = 1.11–1.93). The findings of this study suggest that individuals in this cohort whose parents divorced as children were at greater risk for stroke later in life. Potentially moderating variables were hypothesized, including childhood poverty, sleep hygiene, and hypertension.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127)

A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial

Advancing bat monitoring: Assessing the impact of unmanned aerial systems on bat activity

With the increasing height and rotor diameter of wind turbines, bat activity monitoring within the risk area becomes more challenging. This study investigates the impact of Unmanned Aerial Systems (UAS) on bat activity and explores acoustic bat detection via UAS as a new data collection method in the vicinity of wind turbines. We tested two types of UAS, a multicopter and a Lighter Than Air (LTA) UAS, to understand how they may affect acoustically recorded and analyzed bat activity level for three echolocation groups: Pipistrelloid, Myotini, and Nyctaloid. We hypothesized (i) that the LTA UAS will not affect bat activity levels while a multicopter, due to higher noise emission, might have a negative impact. Our results support this hypothesis, because multicopter flights have a highly significant negative impact on bat activity levels with a medium effect size, particularly for the Myotini (P < 0.001, dm = 0.54) and Nyctaloid group (P < 0.001, dn = 0.55) and a small effect size for the Pipistrelloid group (P < 0.001, dp = 0.36). In contrast, the LTA UAS had no significant effect on bat activity for each echolocation group (P > 0.05 for each group), suggesting its suitability for non-intrusive acoustic monitoring. Furthermore, we hypothesized (ii) that larger UAS propellers prevent the deterrent effect on bats. However, despite the use of larger propellers for the multicopter UAS compared to previous studies, we observed a deterrence effect for all echolocation groups. Additionally, we hypothesized that (iii) any initial deterrence or attraction effect might decrease over time. Our results did not support this hypothesis because we did not observe any habituation of bats to UAS within the 15-minute flight period. Our study highlights the potential of UAS for bat monitoring but underscores the critical importance of selecting appropriate UAS types and operating noise levels for successful surveillance efforts.

Unraveling the distinctive gut microbiome of khulans (Equus hemionus hemionus) in comparison to their drinking water and closely related equids

Abstract The microbial composition of host-associated microbiomes is influenced by co-evolutionary interactions, host genetics, domestication, and the environment. This study investigates the contribution of environmental microbiota from freshwater bodies to the gastrointestinal microbiomes of wild khulans (Equus hemionus hemionus, n = 21) and compares them with those of captive khulans (n = 12) and other equids—Przewalski’s horse (n = 82) and domestic horse (n = 26). Using PacBio technology and the LotuS pipeline for 16S rRNA gene sequencing, we analyze microbial diversity and conduct differential abundance, alpha, and beta diversity analyses. Results indicate limited microbial sharing between wild khulans and their waterhole environments, suggesting minimal environmental influence on their gut microbiomes and low levels of water contamination by khulans. Wild khulans exhibit greater microbial diversity and richness compared to captive ones, likely due to adaptations to the harsh nutritional conditions of the Gobi desert. Conversely, captive khulans show reduced microbial diversity, potentially affected by dietary changes during captivity. These findings highlight the significant impact of environment and lifestyle on the gut microbiomes of equids.

Dual-channel near-field holographic MIMO communications based on programmable digital coding metasurface and electromagnetic theory

Proper 5’-3’ cotranslational mRNA decay in yeast requires import of Xrn1 to the nucleus

The budding yeast Xrn1 protein shuttles between the nucleus, where it stimulates transcription, and the cytoplasm, where it executes the major cytoplasmic mRNA decay. In the cytoplasm, apart from catalyzing 5’→3’ decay onto non translated mRNAs, Xrn1 can follow the last translating ribosome to degrade the decapped mRNA template, a process known as “cotranslational mRNA decay”. We have previously observed that the import of Xrn1 to the nucleus is required for efficient cytoplasmic mRNA decay. Here by using an Xrn1 mutant that cannot enter the nucleus, but is otherwise functional in ribonuclease activity, we show that nuclear import is necessary for proper global cotranslational decay of mRNAs along coding regions and also affects degradation in the of 5’ region of a large group of mRNAs, which comprise about 20% of the transcriptome. Furthermore, a principal component analysis of the genomic datasets of this mutant and other Xrn1 mutants also shows that lack of a cytoplasmic 5’→3’ exoribonuclease is the primary cause of the physiological defects seen in a xrn1Δ mutant, but also suggests that Xrn1 import into the nucleus is necessary for its full in vivo functions.

A comparative machine learning study of schizophrenia biomarkers derived from functional connectivity

Abstract Functional connectivity holds promise as a biomarker of schizophrenia. Yet, the high dimensionality of predictive models trained on functional connectomes, combined with small sample sizes in clinical research, increases the risk of overfitting. Recently, low-dimensional representations of the connectome such as macroscale cortical gradients and gradient dispersion have been proposed, with studies noting consistent gradient and dispersion differences in psychiatric conditions. However, it is unknown which of these derived measures has the highest predictive capacity and how they compare to raw functional connectivity specifically in the case of schizophrenia. Our study evaluates which connectome features derived from resting state functional MRI — functional connectivity, gradients, or gradient dispersion — best identify schizophrenia. To this end, we leveraged data of 936 individuals from three large open-access datasets: COBRE, LA5c, and SRPBS-1600. We developed a pipeline which allows us to aggregate over a million different features and assess their predictive potential in a single, computationally efficient experiment. We selected top 1% of features with the largest permutation feature importance and trained 13 classifiers on them using 10-fold cross-validation. Our findings indicate that functional connectivity outperforms its low-dimensional derivatives such as cortical gradients and gradient dispersion in identifying schizophrenia (Mann–Whitney test conducted on test accuracy: connectivity vs. 1st gradient: U = 142, p < 0.003; connectivity vs. neighborhood dispersion: U = 141, p = 0.004). Additionally, we demonstrated that the edges which contribute the most to classification performance are the ones connecting primary sensory regions. Functional connectivity within the primary sensory regions showed the highest discrimination capabilities between subjects with schizophrenia and neurotypical controls. These findings along with the feature selection pipeline proposed here will facilitate future inquiries into the prediction of schizophrenia subtypes and transdiagnostic phenomena.

Author Correction: Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster

Construction of the national fitness public service satisfaction model in China based on American Customer Satisfaction Index

Objective The national fitness initiative in China is a strategic priority, public satisfaction is a key metric for evaluating the effectiveness of public services. The American Customer Satisfaction Index (ACSI) model has proven a robust tool for evaluating satisfaction with public services. The objective of study was to construct a satisfaction model for national fitness public services in China based on the ACSI framework and to explore the complex relationships among its components. Methods Evaluation dimensions and an item pool were carefully developed by referencing the ACSI model and relevant academic literature. After a panel of experts assessed the initial items pool, the study formed the questionnaire to distribute the residents in Guangzhou, a total of 1,133 valid responses were collected. Data analysis was conducted using SPSS 22.0 and AMOS 16.0 software to evaluate the reliability and validity of the measurement model, the goodness-of-fit of the structural model, and analyze the statistical significance of each path coefficient. Results Public expectation does not directly influence satisfaction (path coefficient 0.039, p = 0.103), it exerts a significant and direct influence on perceived quality (path coefficient 0.445, p = 0.003), which in turn demonstrably shapes public satisfaction (path coefficient 0.403, p = 0.005). Perceived quality also directly influences perceived value (path coefficient 0.735, p = 0.006), which in turn significantly impacts public satisfaction (path coefficient 0.554, p = 0.003). Public satisfaction directly and significantly influences both public complaints (path coefficient 0.395, p = 0.003) and public trust (path coefficient 0.699, p = 0.003). Conclusion Perceived quality is the most critical factor influencing public satisfaction, which subsequently affects public complaints and trust. Fitness service providers should consistently improve service quality, aligning actual service delivery with public expectations, and enhancing the perceived value for the public. These efforts will bolster the public’s satisfaction level.

Association between phase angle and all-cause mortality in adults aged 18–49 years: NHANES 1999–2004

The molecular basis of Human FN3K mediated phosphorylation of glycated substrates

Abstract Glycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of the target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However, the molecular basis of this relationship has not been explored so far. Here, we determined a series of crystal structures of HsFN3K in the apo-state, and in complex with different nucleotide analogs together with a sugar substrate mimic to reveal the features important for its kinase activity and substrate recognition. Additionally, the dynamics in sugar substrate binding during the kinase catalytic cycle provide important mechanistic insights into HsFN3K function. Our structural work provides the molecular basis for rational small molecule design targeting FN3K.

The impact of social networks on rural residents’ engagement in living environment upgrade: An integrated analysis drawing on social network theory and the theory of planned behavior

The issue of rural living environment is a critical concern for China and the global community, intricately intertwined with regional economic development. The proactive involvement of rural residents, who are both beneficiaries and influencers of the environment, constitutes a cornerstone in improving environmental standards. Therefore, the factors that shape rural residents’ participation in living environment upgrade must be explored. Drawing upon the theory of planned behavior and social capital theory, this study employs a structural equation model (SEM) to comprehensively examine the determinants of rural residents’ engagement in living environment upgrade, utilizing data from 334 households in Hebei Province, China. The findings can be summarized as follows: (1) Social networks, subjective norms, perceived behavioral control, and attitudes towards behavior significantly and positively impact rural residents’ engagement in upgrading the living environment, (2) Attitudes towards behavior act as mediators between perceived behavioral control and rural residents’ engagement in living environment upgrade, as well as between subjective norms and rural residents’ engagement in living environmental upgrade. (3) Social networks could indirectly influence rural residents’ engagement in living environment upgrade through the independent mediating effect of subjective norms and attitudes towards behavior, as well as through the chain mediating effect of the two. In conclusion, several managerial recommendations are proposed to stimulate rural residents’ active participation in living environment upgrade.

Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis

Abstract The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro. A comprehensive analysis of compounds from the ChemDiv and PubChem databases was performed. The physicochemical properties, pharmacokinetics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles were evaluated to determine drug similarity and safety. Compound 4896 − 4038 proved to be the most promising candidate. It exhibited a favorable balance between molecular weight (491.06) and lipophilicity (logP 3.957), high intestinal absorption (92.119%), and broad tissue distribution (VDss of 0.529), indicating good oral bioavailability and therapeutic potential. Molecular docking studies showed that 4896 − 4038 has a strong binding affinity to the active site of Mpro and forms key interactions, such as hydrogen bonds, carbon-hydrogen bonds, pi-sulfur, and multiple van der Waals and pi-pi stacked bonds. The binding energy was comparable to that of the reference drug X77, indicating potential efficacy. Molecular dynamics simulations over 300 ns confirmed the stability of the Mpro/4896 − 4038 complex of protein-ligand. Free energy landscape mapping and MM/PBSA calculations further substantiated the favorable binding and stability of the complex. Importantly, 4896 − 4038 exhibited a comparatively favorable safety profile. In summary, compound 4896 − 4038 shows significant potential as a potent SARS-CoV-2 Mpro inhibitor, combining potent inhibitory activity with favorable pharmacokinetic and safety profiles. These results support the further development of 4896 − 4038 as a promising therapeutic agent in the fight against COVID-19 that warrants experimental validation and clinical investigation.

Promoting in-situ stability of hydroxide exchange membranes by thermally conductive network for durable water electrolysis

What emotions does music express? Structure of affect terms in music using iterative crowdsourcing paradigm

Music is assumed to express a wide range of emotions. The vocabulary and structure of affects are typically explored without the context of music in which music is experienced, leading to abstract notions about what affects music may express. In a series of three experiments utilising three separate and iterative association tasks including a contextualisation with typical activities associated with specific music and affect terms, we identified the plausible affect terms and structures to capture the wide range of emotions expressed by music. The first experiment produced a list of frequently nominated affect terms (88 out of 647 candidates), and the second experiment established and confirmed multiple factor structures, ranging from 21, to 14, and 7 dimensions. The third experiment compared the terms with external datasets looking at discrete emotions and emotion dimensions, which verified the 7-factor structure and identified a compact 4-factor structure. These structures of affects expressed by music did not conform to music-induced emotion structures, nor could they be explained by basic emotions or affective circumplex. The established affect structures were largely positive and contained concepts such as “romantic” and “free”, and terms such as “in love”, “dreamy”, and “festive” that have rarely featured in past research.