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Abstract Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.

The Bayesian piecewise growth model (PGM) is a useful class of models for analyzing nonlinear change processes that consist of distinct growth phases. In applications of Bayesian PGMs, it is important to accurately capture growth trajectories and carefully consider knot placements. The presence of missing data is another challenge researchers commonly encounter. To address these issues, one could use model fit and selection indices to detect misspecified Bayesian PGMs, and should give care to the potential impact of missing data on model evaluation. Here we conducted a simulation study to examine the impact of model misspecification and missing data on the performance of Bayesian model fit and selection indices (PPP-value, BCFI, BTLI, BRMSEA, BIC, and DIC), with an additional focus on prior sensitivity. Results indicated that (a) increasing the degree of model misspecification and amount of missing data aggravated the performance of indices in detecting misfit, and (b) different prior specifications had negligible impact on model assessment. We provide practical guidelines for researchers to facilitate effective implementation of Bayesian PGMs.

Abstract Under transient greenhouse warming, El Niño-Southern Oscillation (ENSO) is projected to increase pre-2100, accompanied by an easier establishment of atmospheric convection in the equatorial eastern Pacific, where sea surface temperature (SST) warms faster than surrounding regions. After 2100, how ENSO variability may change remains unknown. Here we find that under a high emission scenario, ENSO variability post-2100 reverses from the initial increase to an amplitude far smaller than that of the 20th century. The fast eastern warming persists and shrinks the equatorial Pacific non-convective area, such that establishing convection in the non-convective area, as during an El Niño, requires smaller convective anomaly, inducing weaker wind anomalies leading to reduced ENSO SST variability. The nonlinear ENSO response is thus a symptom of the persistent El Niño-like warming pattern. Therefore, the oscillatory ENSO impact could be replaced by that from the permanent El Niño-like mean condition with cumulative influences on affected regions.

Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO−) species and limit the therapeutic effect of NO. Hence, we design a ROS-responsive NO nanomedicine (t-PBA&NO NP) with ROS scavenging ability to solve the dilemma of NO-based therapy. t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate (ECA) to the injury sites via collagen IV homing peptide. The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging, endoplasmic reticulum and mitochondrial regulation. It subsequently maximizes vascular modulation effects of NO, without production of harmful compounds, reactive nitrogen species (RNS). Therefore, it significantly increases competitiveness of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) both in vitro and in vivo. The strategy proved effective in inducing faster re-endothelialization, inhibiting neointimal formation and restoring vascular homeostasis. The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.

Abstract Background Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading. Methods Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI). Results Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17+ GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils. Conclusions Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17+ GBC cells in GBC-LI.

The vacancy and helium effects on eight low-Σ symmetric tilt grain boundaries (STGBs) of Ni were investigated by first-principles calculations. The simulations demonstrate that vacancies in Ni matrix could diffuse easily to the grain boundary and helium atoms are quite stable at the grain boundary vacancy sites. Vacancy accumulation at high-energy STGBs could enhance the binding strength while He defects are generally detrimental to grain boundary binding and interstitial helium defects can initiate more severe grain boundary cracking comparing to vacancy-bind-helium. Further electron charge analysis suggested the influence of grain boundary binding greatly relies on the grain boundary atomic structure and the interaction between Ni-d and He-p states. The polarized charge transfer induced by He helium occupation was predicted to be detrimental to the binding strength, which explains the experimentally-observed helium bubbles and helium-induced GB embrittlement.

Objective: This study aimed to analyze research on anxiety disorders using VOSviewer and CiteSpace to identify research hotspots and future directions. Methods: We conduct ed a comprehensive search on the Web of Science Core Collection (WoSCC) for relevant studies about anxiety disorders published within the past two decades (from 2004 to 2024). VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 22,267 publications related to anxiety disorders were retrieved. The number of publications about anxiety disorders has generally increased over time, with some fluctuations. The United States emerged as the most productive country, with Harvard University identified as the most prolific institution and Brenda W. J. H. Penninx as the most prolific author in the field. Conclusion: This research identified the most influential publications, authors, journals, institutions, and countries in the field of anxiety research. Future research directions are involved advanced treatments based on pharmacotherapy, psychotherapy and digital interventions, mechanism exploration to anxiety disorders based on neurobiological and genetic basis, influence of social and environmental factors on the onset of anxiety disorders.

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials.

Rationale Nontuberculous mycobacteria (NTM) has been reported to be transmitted between people with cystic fibrosis (CF) attending CF centres. A suspected Mycobacterium abscessus outbreak was investigated at the University of Texas Southwestern (UTSW) Adult CF Program using a combination of pathogen genomic sequencing and epidemiologic methods. The objectives of the present study were to apply the Healthcare-Associated Links in Transmission of NTM (HALT NTM) study to investigate the occurrence of potential healthcare-associated transmission and/or acquisition of NTM among people with CF infected with genetically similar NTM isolates. Methods Whole-genome sequencing of respiratory M. abscessus isolates from 50 people with CF receiving care at UTSW was performed to identify genetically similar isolates. Epidemiologic investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping were studied. Measurements and main results Whole-genome sequencing analysis demonstrated seven clusters of genetically similar M. abscessus (four ssp. abscessus and three ssp. massiliense). Epidemiologic investigation revealed potential opportunities for healthcare-associated transmission within three of these clusters. Healthcare environmental sampling did not recover M. abscessus, but did recover four human disease-causing species of NTM. No subjects having clustered infections lived in the same home residence watershed. Some subjects were infected with more than one M. abscessus genotype, both within and outside of the dominant circulating clones. Conclusions Healthcare-associated person-to-person transmission of M. abscessus appears to be rare at this centre. However, polyclonal infections of M. abscessus species and subspecies, not originating from the endemic hospital environment, suggest multiple shared modes of acquisition outside the healthcare setting.

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection—those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many high-priority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy.

Abstract Despite the worldwide distribution and rich diversity of the superfamily Tenebrionoidea, the knowledge of the mitochondrial genomes (mtgenome) characteristics of the superfamily is still very limited, and its phylogenetics and evolution remain unresolved. In the present study, we newly sequenced mtgenomes from 19 species belonging to Tenebrionoidea, and a total of 90 mitochondrial genomes from 16 families of Tenebrionoidea were used for phylogenetic analysis. There exist 37 genes for all 82 species of complete mtgenomes of 16 families investigated, and their characteristics are identical as reported mtgenomes of other Tenebrionoids. The Ka/Ks analysis suggests that all 13 PCGs have undergone a strong purifying selection. The phylogenetic analysis suggests the monophyly of Mordellidae, Meloidae, Oedemeridae, Pyrochroidae, Salpingidae, Scraptiidae, Lagriidae, and Tenebrionidae, and the Mordellidae is close to the Ripiphoridae. The “Tenebrionidae clade” and “Meloidae clade” are monophyletic, and both of them are sister groups. In the “Meloidae clade,” Meloidae is close to Anthicidae. In the “Tenebrionidae clade,” the family Lagriidae and Tenebrionidae are sister groups. The divergence time analysis suggests that Tenebrionoidea originated in the late Jurassic, Meloidae Mordellidae, Lagriidae, and Tenebrionidae in the Cretaceous, Oedemeridae in Paleogene. The work lays a base for the study of mtgenome, phylogenetics, and evolution of the superfamily Tenebrionoidea.

BackgroundEpilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations.MethodsWe conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas.ResultsA total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including “recognitive impairment” and “mental health,” indicating potential future research hotspots and trends.ConclusionThis study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract- loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds.

Abstract Background Postpartum dysfunctions and complications can occur in women. However, functional assessment should be conducted to make treatment plans before any intervention is implemented. In this context, the International Classification of Functioning, Disability and Health (ICF) may be a useful tool for women postpartum to document functional data and set rehabilitation goals. The purpose of this study was to determine the corresponding domains that should be considered in the evaluation of women’s postpartum functioning based on the International Classification of Functioning, Disability and Health (ICF) model using the Delphi method. Methods Fifteen domestic experts were invited to conduct two rounds of expert consensus survey on the ICF-based postpartum functional assessment category pool obtained through literature retrieval, clinical investigation, and reference to relevant literature. The sample was medical staff with professional knowledge of women’s health. The opinions of experts were summarized, and the positive coefficient, authority coefficient and coordination degree of experts were calculated. Results A total of 15 domestic experts participated in this expert consensus. Through two rounds of a questionnaire survey, 69 items were finally selected to form the ICF-based postpartum functional assessment tool for women. The items included 32 items of body function, 12 items of body structure, 17 items of activity and participation, and 8 items of environmental factors. In addition, we identified 8 items of personal factors. The expert positive coefficients of the two rounds of expert consensus were both 100%, the authority coefficient was 0.789, and the coefficient of variation was between 0.09 to 0.31. Conclusion A postpartum functional assessment tool for women based on the ICF model was constructed based on the Delphi method, which can provide more comprehensive health management and life intervention for postpartum women. Trial registration The Registration number of the Chinese Clinical Trial Registry is ChiCTR2200066163, 25/11/2022.

Saponins are an important class of active components in Chinese herbal medicines (CHMs), which are present in large quantities in Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, Polygonati Rhizoma, etc., and have immune regulation, anti-tumor, anti-inflammatory, anti-cardiovascular disease, and hypoglycemic activities. Storage and processing are essential processes in the production process of CHMs which affect the stability of saponin components and then reduce the medicinal and economic value. Therefore, it is of great importance to investigate the effects of storage and processing conditions on the content of saponin components in CHMs. In this paper, the effects of various storage and processing factors, including temperature, pH, enzymes, meta lions, extraction methods, etc., on the saponin content of CHMs are investigated and the underlying mechanisms for the quantitative changes of saponin are summarized. These findings may provide technical guidance for the production and processing of saponin-rich CHMs.