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Abstract Objective A rapid and accurate forecast for the early prognosis of ICH patients is challenging. This study investigated whether heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) could prognosticate poor neurological outcomes in ICH patients. Methods Between November 2020 and November 2021, we studied 92 spontaneous ICH patients in the First Affiliated Hospital of Nanjing Medical University. Glasgow Outcome Scale (GOS) score at 2 weeks after the ICH was used to categorize patients into good and poor outcome groups. The modified Rankin Scale (mRS) assessed patients' ability to live independently for 1 year. We utilized a portable high‐frequency electrocardiogram (ECG) recording system to record the HRV and SKNA information in ICH patients and control participants. Results 77 patients were eligible for the prediction of neurological outcome and were allocated into the good (n = 22) or poor (n = 55) outcome groups based on the GOS grade. In univariate logistic regression analysis, significant variables that could differentiate the outcomes were age, hypertension, tracheal intubation, Glasgow Coma Scale (GCS) score, existing intraventricular hemorrhage, white blood cells, neutrophil, lnVLF, lnTP, and aSKNA. Variables in the best fit multivariable logistic regression model were age, hypertension, GCS score, neutrophils, and aSKNA. The GCS score was the only independent risk factor for poor outcomes. At 30 days and 1 year of follow‐up, patients with lower aSKNA had poor outcomes. Interpretation ICH patients had reduced aSKNA, which could be a prognostic indicator. A lower aSKNA suggested a worse prognosis. The present data indicate that ECG signals could be helpful for prognosticating ICH patients.

Abstract Background Prevention, screening, and early treatment are the aims of postoperative delirium management. The scoring system is an objective and effective tool to stratify potential delirium risk for patients undergoing cardiac surgery. Methods Patients who underwent cardiac surgery between January 1, 2012, and January 1, 2019, were enrolled in our retrospective study. The patients were divided into a derivation cohort (n = 45,744) and a validation cohort (n = 11,436). The AD predictive systems were formulated using multivariate logistic regression analysis at three time points: preoperation, ICU admittance, and 24 h after ICU admittance. Results The prevalence of AD after cardiac surgery in the whole cohort was 3.6% (2,085/57,180). The dynamic scoring system included preoperative LVEF ≤ 45%, serum creatinine > 100 µmol/L, emergency surgery, coronary artery disease, hemorrhage volume > 600 mL, intraoperative platelet or plasma use, and postoperative LVEF ≤ 45%. The area under the receiver operating characteristic curve (AUC) values for AD prediction were 0.68 (preoperative), 0.74 (on the day of ICU admission), and 0.75 (postoperative). The Hosmer‒Lemeshow test indicated that the calibration of the preoperative prediction model was poor (P = 0.01), whereas that of the pre- and intraoperative prediction model (P = 0.49) and the pre, intra- and postoperative prediction model (P = 0.35) was good. Conclusions Using perioperative data, we developed a dynamic scoring system for predicting the risk of AD following cardiac surgery. The dynamic scoring system may improve the early recognition of and the interventions for AD.

ABSTRACTLattice structure can realize excellent multifunctional characteristics because of its huge design space, and the cellular configuration directly affects the lattice structural performance and lightweight. A novel energy-absorbing multifunctional lattice structure with phononic bandgap is presented by topology and parameter optimization in this paper. First, the two-dimensional (2D) cellular configuration is lightweight designed by using independent continuous mapping (ICM) topology optimization method. The 2D cell is reconstructed by geometric parameters and rotated into a three-dimensional (3D) cell by using chiral shape to achieve bandgap. Subsequently, the surrogated model with energy absorption as the object and first-order natural frequency as the constraint is established to optimize a parametric 3D cell based on the Response Surface Methodology (RSM). Finally, the lattice structures are assembled with dodecagonal staggered arrangements to avoid the deformation interference among the adjacent cells. In addition, the lattice structural energy absorption and bandgap characteristics are analyzed and discussed. Compared to Kelvin lattice structure, the optimal lattice structure shows significant improvement in energy absorption efficiency. Besides, the proposed design also performs well in damping characteristics of the high-frequency and wide-bandgap. The lattice structural optimization design framework has great meaning to achieve the equipment structural lightweight and multi-function in the aerospace field.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Abstract Background The relationship between obesity and hearing loss among the middle-aged and older population remained unclear. Moreover, few studies have focused on the impact of gender on this association. Methods This cohort study extracted the data from the China Health and Retirement Longitudinal Study, a national survey of adults aged 45 years or over. Waist circumference was categorized into three groups: normal, pre-central obesity, and central obesity. We classified BMI into four categories: underweight, normal weight, overweight, and obese. The primary endpoint was the incidence of self-reported hearing loss. Results Of the 14,237 participants, 1972 incidents of hearing loss were identified during a median 6.9 years of follow-up. The cumulative incidence of hearing loss was 13.9% (95% CI 13.3% -14.4%). Our study showed that central obesity was significantly associated with hearing loss (HR 0.84, 95%CI 0.75–0.94), and this relationship was more prominent in males (HR 0.76, 95%CI 0.63–0.91). Among male participants, the underweight group was at the highest risk of hearing loss (HR 1.39, 95%CI 1.08–1.79). Compared with the normal weight group, the adjusted HR for hearing loss in the obese groups was 0.69 (95%CI 0.51–0.94) among men. Among female participants, only the overweight group had a lower risk of hearing loss than the normal weight group (HR 0.83, 95%CI 0.71–0.96). Conclusions Being overweight and obese were significantly associated with a decreased risk of hearing loss, whereas being underweight was associated with an increased risk of hearing loss.

Background: Homologous recombination deficiency (HRD) phenotype will sensitize tumors to poly (ADP-ribose) polymerases inhibitors and platinum. However, previous studies did not focus on the prevalence of HRD among Chinese breast cancer (BC) patients. Methods: One hundred and forty-seven BC patients were included in this study. Their HRD status was assessed by Genomic Scar Score (GSS), which was determined according to the length, site, and type of copy number. HRD was defined as positive when a harmful BRCA1/2 mutation was detected or GSS ≥50. Results: Our data revealed that 9.5% of the 147 patients tested positive for BRCA1/2 mutation, while approximately 34.7% were HRD-positive. For triple negative BC (TNBC), HRD positivity rate (60.5%) was higher than Luminal A (5.3%), Luminal B (HER2-) (28.8%), and Luminal B (HER2+) (31.6%) subgroups. HRD-positive tumors were more likely to be ER/PR-negative and exhibited higher Ki-67 expression. 50.0% of the HRD-positive patients achieved pathologic complete remission (pCR) after neoadjuvant therapy. HRD-positive patients tended to have a higher risk for cancer recurrence or metastasis compared to HRD-negative patients (29.4% vs. 13.5%). Conclusion: We investigated the HRD status among Chinese BC patients using an HRD detection tool developed based on the Chinese population. The clinical characteristics, pathological profile, family history pattern, neoadjuvant efficacy, and disease progression events of HRD-positive and negative patients were described and compared. Thus, our data provided an evidence-based basis for applying the original HRD assay in Chinese BC.

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.

Abstract Background The study objective was to validate the relative biological effectiveness (RBE) calculated by the modified microdosimetric kinetic model in RayStation (Ray-MKM) for active-energy scanning carbon-ion radiotherapy. Methods The Ray-MKM was benchmarked using a spread-out Bragg-peak (SOBP) plan, which was suggested in literature from the National Institute of Radiobiological Science (NIRS) in Japan. The residual RBE differences from the MKM at NIRS (NIRS-MKM) were derived using several SOBP plans with different ranges, SOBP widths, and prescriptions. To investigate the origins of the differences, we compared the saturation-corrected dose-mean specific energy $$Z_{1D}^{*}$$ Z 1 D ∗ of the aforementioned SOBPs. Furthermore, we converted the RBE-weighted doses with the Ray-MKM to those with local effect model I (LEM doses). The purpose was to investigate whether the Ray-MKM could reproduce the RBE-weighted conversion study. Results The benchmark determined the value of the clinical dose scaling factor, $$F_{clin}$$ F clin , as 2.40. The target mean RBE deviations between the Ray-MKM and NIRS-MKM were median: 0.6 (minimum: 0.0 to maximum: 1.69) %. The $$Z_{1D}^{*}$$ Z 1 D ∗ difference in-depth led to the RBE difference in-depth and was remarkable at the distal end. The converted LEM doses from the Ray-MKM doses were comparable (the deviation being − 1.8–0.7%) to existing literature. Conclusion This study validated the Ray-MKM based on our active-energy scanning carbon-ion beam via phantom studies. The Ray-MKM could generate similar RBEs as the NIRS-MKM after benchmarking. Analysis based on $$Z_{1D}^{*}$$ Z 1 D ∗ indicated that the different beam qualities and fragment spectra caused the RBE differences. Since the absolute dose differences at the distal end were small, we neglected them. Furthermore, each centre may determine its centre-specific $$F_{clin}$$ F clin based on this approach.

The concept of single-valued neutrosophic sets (SVNSs) is considered as an attractive tool for dealing with highly ambiguous and uncertain information. The correlation coefficient of SVNSs acts as an important measure in the single-valued neutrosophic set theory and it has been applied in various fields, such as the pattern recognition, medical diagnosis, decision-making and also clustering analysis. To alleviate the weakness of the existing correlation coefficients, a novel statistical correlation coefficient is put forward to measure the degree of correlation between two SVNSs. This statistical correlation coefficient is developed based on the variance and covariance of SVNSs and its value is between −1 and 1. When solving the multicriteria decision making problems, the criteria show different weight values. To consider the weight information of multiple criteria, the weighted statistical correlation coefficient is developed for SVNSs. Afterwards, two numerical examples are given to show the effectiveness of the proposed statistical correlation coefficient in the pattern recognition, which can accurately classify unknown patterns into known patterns. Finally, the feasibility and practicability of the proposed correlation coefficient formula are illustrated by a practical multiple attribute decision making problem of traditional Chinese medicine diagnosis. The comparative results show that the proposed correlation coefficient formula is rational and effective.

Abstract Acoustic cardiography is a completely new technology, it has great advantages in the rapid diagnosis of cardiovascular diseases. The purpose of this study was to investigate the clinical value of the fourth heart sound (S4), cardiac systolic dysfunction index (SDI), and the cardiac cycle time-corrected electromechanical activation time (EMATc) in the prediction of post-percutaneous coronary intervention (PCI) early ventricular remodeling (EVR) in patients with acute myocardial infarction (AMI). We recruited 161 patients with AMI of 72-h post-PCI, including 44 EVR patients with left ventricular ejection fraction (LVEF)

[This corrects the article DOI: 10.1371/journal.pone.0303858.].

ObjectiveThe study aims to explore the driving forces behind physical activity engagement among patients with chronic obstructive pulmonary disease, focusing on motivation, opportunity, and capability.DesignA phenomenological qualitative study applied the motivation, opportunity, and capability model, conducted in two respiratory units of a Chinese university hospital.MethodsParticipants, selected by age, gender, and illness duration, included inpatients during the interview sessions and those recently discharged within six months. One-on-one semi-structured interviews were recorded, transcribed, and analyzed by the Colaizzi seven-step method.ResultsSeventeen participants diagnosed with chronic obstructive pulmonary disease for over one year aged between 66 (range: 42-96) participated. Three major themes were identified: Inspiring participation motivation-transitioning from recognizing significance to habit formation; Offering participation opportunities-reiterating demand for personalized strategies and ideal environmental settings; Enhancing participation capability-addressing strategies for overcoming fears, setting goals, ensuring safety, and adjusting activity levels.ConclusionsThis research underscores the vital role of inspiring participation motivation, offering opportunities, and enhancing the capability for participation in effective engagement. Advocating increased attention from healthcare departments, fostering interdisciplinary collaboration, improving activity guidance and counseling effectiveness, and considering individual preferences can significantly benefit those patients with chronic obstructive pulmonary disease who hesitate or are unable to participate in physical activities, thereby increasing the dose of non-leisure time physical activity.

ObjectiveHand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis.MethodsWe performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software.Results21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo.ConclusionsIn summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative.

Bone marrow-derived CD34-positive (CD34+) endothelial progenitor cells (EPCs) has unique functions in the mechanism of compensatory lung growth (CLG). The content of this study is mainly to describe the effect of microRNA (miR)-155 in the mechanisms of EPCs and CLG. Our study found that transfection of miR-155 mimic could promote EPC proliferation, migration and tube formation, while transfection of miR-155 inhibitor had the opposite effect. It was also found that transfection of pc-JARID2 inhibited EPC proliferation, migration and tube formation, while transfection of si-JARID2 had the opposite effect. miR-155 can target and negatively regulate JARID2 expression. Overexpression of JARID2 weakened the promoting effects of miR-155 mimic on EPC proliferation, migration, and tubular formation, while silencing JARID2 weakened the inhibitory effects of miR-155 inhibitors on EPC proliferation, migration, and tubular formation. Transplantation of EPCs transfected with miR-155 mimic into the left lung model effectively increased lung volume, total alveolar number, diaphragm surface area, and lung endothelial cell number, while transplantation of EPCs co-transfected with miR-155 mimic and pc-JARID2 reversed this phenomenon. Overall, we found that miR-155 activates CD34+ EPC by targeting negative regulation of JARID2 and promotes CLG.

The objectives are to improve the diagnostic efficiency and accuracy of epidemic pulmonary infectious diseases and to study the application of artificial intelligence (AI) in pulmonary infectious disease diagnosis and public health management. The computer tomography (CT) images of 200 patients with pulmonary infectious disease are collected and input into the AI-assisted diagnosis software based on the deep learning (DL) model, "UAI, pulmonary infectious disease intelligent auxiliary analysis system", for lesion detection. By analyzing the principles of convolutional neural networks (CNN) in deep learning (DL), the study selects the AlexNet model for the recognition and classification of pulmonary infection CT images. The software automatically detects the pneumonia lesions, marks them in batches, and calculates the lesion volume. The result shows that the CT manifestations of the patients are mainly involved in multiple lobes and density, the most common shadow is the ground-glass opacity. The detection rate of the manual method is 95.30%, the misdetection rate is 0.20% and missed diagnosis rate is 4.50%; the detection rate of the DL-based AI-assisted lesion method is 99.76%, the misdetection rate is 0.08%, and the missed diagnosis rate is 0.08%. Therefore, the proposed model can effectively identify pulmonary infectious disease lesions and provide relevant data information to objectively diagnose pulmonary infectious disease and manage public health.

Livestock on the Qinghai-Tibetan Plateau is of great importance for the livelihood of the local inhabitants and the ecosystem of the plateau. The natural, harsh environment has shaped the adaptations of local livestock while providing them with requisite eco-services. Over time, unique genes and metabolic mechanisms (nitrogen and energy) have evolved which enabled the yaks to adapt morphologically and physiologically to the Qinghai-Tibetan Plateau. The rumen microbiota has also co-evolved with the host and contributed to the host's adaptation to the environment. Understanding the complex linkages between the rumen microbiota, the host, and the environment is essential to optimizing the rumen function to meet the growing demands for animal products while minimizing the environmental impact of ruminant production. However, little is known about the mechanisms of host-rumen microbiome-environment linkages and how they ultimately benefit the animal in adapting to the environment. In this review, we pieced together the yak's adaptation to the Qinghai-Tibetan Plateau ecosystem by summarizing the natural selection and nutritional features of yaks and integrating the key aspects of its rumen microbiome with the host metabolic efficiency and homeostasis. We found that this homeostasis results in higher feed digestibility, higher rumen microbial protein production, higher short-chain fatty acid (SCFA) concentrations, and lower methane emissions in yaks when compared with other low-altitude ruminants. The rumen microbiome forms a multi-synergistic relationship among the rumen microbiota services, their communities, genes, and enzymes. The rumen microbial proteins and SCFAs act as precursors that directly impact the milk composition or adipose accumulation, improving the milk or meat quality, resulting in a higher protein and fat content in yak milk and a higher percentage of protein and abundant fatty acids in yak meat when compared to dairy cow or cattle. The hierarchical interactions between the climate, forage, rumen microorganisms, and host genes have reshaped the animal's survival and performance. In this review, an integrating and interactive understanding of the host-rumen microbiome environment was established. The understanding of these concepts is valuable for agriculture and our environment. It also contributes to a better understanding of microbial ecology and evolution in anaerobic ecosystems and the host-environment linkages to improve animal production.

Abstract Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long‐term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l‐lactic acid)–gelatin–A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein‐derived peptides (A5G81) to the surface of polydioxanone and poly (l‐lactic acid) fibers. The polymer microfiber–biomacromolecule–peptide frame with biophysical and biochemical cues could orchestrate the biomaterial–host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti‐inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell–biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell–material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

ABSTRACT: Xylooligosaccharide (XOS) is known as a prebiotic, however, it is unknown whether XOS can directly protect against bacterial infection. This study aimed to investigate the direct inhibitory effects of XOS on Salmonella Typhimurium colonization and the inductive impairments in gut health and growth performance in broilers. We first probed the inhibitory effects of XOS on S. Typhimurium adhesion and its induction of intestinal epithelial cell (IPEC-J2) injuries. Afterward, 168 one-day-old yellow-feathered broilers were randomly divided into 3 groups (7 replicates/group): negative control (NC, received a basal diet), positive control (PC, received a basal diet with S. Typhimurium challenge) and XOS group (PC birds + 1,500 mg/kg XOS). All birds except those in NC were orally challenged with S. Typhimurium from 8 to 10 d of age. Parameters were analyzed on d 11. The results showed that XOS inhibited S. Typhimurium adhesion and the inductive injuries of IPEC-J2 cells by lowering (P < 0.05) certain adhesion-related genes expression of this bacterium. It also alleviated S. Typhimurium-induced increase (P < 0.05) in the expression of certain inflammatory cytokines and tight junction (TJ) proteins of IPEC-J2 cells. Supplementing XOS to S. Typhimurium-challenged broilers attenuated the elevations (P < 0.05) in S. Typhimurium colonization of ileal mucosa and its translocation to the liver and spleen, as well as increased (P < 0.05) certain TJ proteins expression of ileum. Besides, XOS addition normalized S. Typhimurium-induced impairments (P < 0.05) in ileal morphology, final body weight and average daily gain in broilers. Collectively, supplemental XOS directly suppressed intestinal colonization of S. Typhimurium by diminishing its adhesiveness and subsequently mitigated destructions in intestinal barriers, thus contributing to weaken growth retardation in challenged broilers. Our findings provide a new insight into the mechanisms of XOS limiting Salmonella infection in chickens.

Abstract Neurostimulation has emerged as a potential remedy for early mild cognitive impairment (EMCI). However, further exploration is needed on how external stimulation of brain regions promotes the transition of the brain state from EMCI to health and the selection of target locations. In this study, a functional magnetic resonance imaging dataset was used to evaluate the brain states of healthy individuals and patients with EMCI to explore the probabilistic metastable substate space, identifying abnormal manifestations of EMCI. Stimulation targets were then identified and stimulated to achieve complete controllability of the effective connection network for EMCI. A whole‐brain model successfully fitted the brain state of the patients with EMCI based on diffusion tensor imaging data. Based on this whole‐brain model, stimulation of the hippocampus, medial frontal gyrus, suboccipital gyrus, and fusiform gyrus can promote the transformation of the brain state from EMCI to health. The findings reveal the underlying brain mechanisms of cognitive decline in patients with EMCI and the stimulation targets of the neural mechanisms of EMCI restoration, which could help in designing more effective therapeutic interventions for EMCI.

Key clinical message Here we reported a particular case of MUTYH‐associated polyposis (MAP) that had only one rare heterozygous variant, but some particular clinical manifestations contributed to occur in this male patient by only one defective MUTYH allele were worth of further investigation. We reported a case of MAP. It is about a 33‐year‐old man with chief complaints of hematochezia who had multiple polyps that were found in his colon via colonoscopy. He followed his doctor's advice and performed a genetic analysis examination. Germline test was positive for a major heterozygous variant: chr1:45800165 on the MUTYH gene. MUTYH gene sequence analysis confirmed the following heterozygous variant: c.55CT (p.R19X) in exon 2 (ClinVar NM_001128425). Unfortunately, his mother and daughter have the ILK variant according to genetic analysis. However, this variant at the site was not detected in his father. Various types of polyps were found on repeated colonoscopy, which tended to become latent cancerous in the future. This case indicated that awareness of the risk of carcinogenesis of polyps in carriers of monoallelic variants might accordingly increase, and our understanding of the type of genetically related disease will be enhanced by us.

Objectives To investigate the prevalence, awareness, treatment and control of dyslipidaemia and its associated factors in eastern China.Design Cross-sectional study.Setting Data were collected from the 2017 Nanjing Chronic Disease and Risk Factor Surveillance.Participants This study included 60 283 participants aged ≥18 years.Outcome measures Prevalence of dyslipidaemia was defined as self-reported history of dyslipidaemia and/or the use of lipid-lowering medication, and/or meeting at least one of the following during on-site investigation: total cholesterol ≥6.2 mmol/L, triglyceride ≥2.3 mmol/L, low-density lipoprotein cholesterol ≥4.1 mmol/L and high-density lipoprotein cholesterol

The rural collective economy plays a crucial role in achieving the common prosperity of farmers, revitalizing the countryside, and modernizing agriculture in China. This paper analyses the impact and internal mechanism of the policy on the level of common prosperity, using provincial panel data from China from 2011 to 2020. Additionally, it investigates whether the rapid development of the rural collective economy takes into account both economic growth and income distribution. The findings demonstrate that the policy significantly enhances the common prosperity of farmers and rural areas. These conclusions remain valid even after considering the endogeneity problem and conducting robustness tests using the time-varying difference-in-differences model. Furthermore, the intermediary effect model reveals that the increase in the rate of farmland transfer and the proportion of scale operation play crucial roles in transmitting the benefits of the policy to achieve common prosperity. The result of the heterogeneity analysis indicates that the marginal decline of policy effect has a greater impact on the enhancement of rural collective economy in the less developed provinces of the central and western regions in China, compared to the developed provinces of the eastern region. These findings have targeted policy significance for promoting the sustainable development of agricultural and rural areas.

Objective This study aimed to investigate the associations between osteoporosis, biochemical indexes, bone mineral density (BMD), and cardiovascular disease. Methods A cross-sectional study design was used to examine the relationships between these parameters. Logistic regression and correlation analyses were conducted to assess the associations between elevated levels of triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), homocysteine, and the presence of osteoporosis. Additionally, correlations between BMD and biochemical indexes were analyzed. The incidence of cardiovascular disease and its correlation with BMD were evaluated. Receiver operating characteristic (ROC) analysis was performed to determine the utility of BMD in identifying cardiovascular disease. Results The results revealed that elevated triglyceride, total cholesterol, and LDL levels were positively associated with osteoporosis, while higher HDL levels and homocysteine were negatively associated. Correlation analysis demonstrated negative correlations between triglyceride levels and BMD, and positive correlations between total cholesterol and HDL levels with BMD. LDL levels showed a weak negative correlation, and homocysteine levels exhibited a strong negative correlation with BMD. The osteoporosis group had lower BMD and a higher incidence of cardiovascular disease compared to the non-osteoporosis group. Logistic regression analysis confirmed the correlation between lower BMD and increased risk of cardiovascular disease. Conclusion This study provides evidence supporting the associations between osteoporosis, biochemical indexes, BMD, and cardiovascular disease. Aberrations in lipid profiles and homocysteine levels may contribute to osteoporosis development. Lower BMD, particularly in individuals with osteoporosis, appears to increase the risk of cardiovascular disease. BMD shows promise as a diagnostic tool for identifying individuals at risk of cardiovascular disease. Further research is needed to elucidate the underlying mechanisms and establish the clinical implications of these relationships. Future longitudinal studies are necessary to determine causality and long-term prognostic implications.

Long-term waterproofing and water leakage treatment of existing underground structures have become prominent issues in the operation and maintenance of underground structures. The use of single organic or inorganic materials for water leakage treatment is not effective for solving practical engineering problems. Considering the properties of organic and inorganic materials, a novel composite material mixing the waterborne epoxy resin and superfine ordinary Portland cement-sulphoaluminate cement was presented, which was studied as a polymer-modified cementitious composite for waterproofing and plugging. This study investigated the primary physical properties of the raw materials of the polymer-modified cementitious composite. Experimental tests were performed to investigate the effects of waterborne epoxy resin on the impermeability, interface adhesion, and tensile deformation performances of the superfine cementitious waterproof material. The results showed that the average water penetration height of the waterborne epoxy resin-modified material was only 52.2% that of the cementitious materials, indicating better impermeability performance. When 3% waterborne epoxy resin was mixed, the bending bond strength of the polymer-modified composite material was 10.6% higher than that of the cementitious material. The direct tensile bond strength of the polymer-modified composite material with various waterborne epoxy resin content significantly improved, demonstrating a maximum increase of 72.6%. Compared with the original cementitious material, the toughness, tensile deformation capacity, and tensile strength of the polymer-modified superfine cementitious composite material were improved. The maximum tensile amount increased by 48.3% when an appropriate amount of waterborne epoxy resin was mixed, which is the primary performance in long-term waterproofing. Moreover, the bearing capacity increased by 335.2% compared with the cementitious materials when 7% waterborne epoxy resin was mixed. The key contribution of this research is to propose a high performance and effective polymer-modified composite material for the treatment of waterproofing and plugging. The findings from the study also provide industry practitioners with a comprehensive guide regarding the mechanical and impermeability performances of the polymer-modified superfine cementitious composite material.

Bisphenol S (BPS) is a raw material that is used extensively in various manufacturing processes but possesses a high detection rate in human red blood cells (RBCs). Accordingly, BPS is a potential toxicant in disturbing the function of RBCs and causing RBC-related diseases. To date, the effects and mechanisms of BPS-induced RBC-related diseases have not been elucidated. Here, using different models, including rats, zebrafish embryos and RBCs, the underlying mechanism of RBC-related diseases induced by BPS was explored. The accumulation of BPS in tissue was colon > kidney > liver > plasma > testicle > heart > brain in SD rats orally administered BPS (10 and 50 mg/kg bw/day) for 32 days, which was similar in both 10 mg/kg bw/day and 50 mg/kg bw/day group. Rats given BPS orally developed hyperlipidemia and increased RBC membrane cholesterol, as well as changes in RBC morphology and function. Moreover, BPS at the concentrations measured in rats plasma caused oxidative stress and phosphatidylserine exposure in vitro RBCs. These combined factors led to RBC aggregation in blood and an increasing in the number of RBCs in the blood vessels of the liver in rats. The dynamic visual observation of RBCs in vein vessels of zebrafish embryos exposed to BPS at 0, 1, 10 and 100 μg/L further found that the flow of RBCs in the tail vein is slow or even immobile, posing the risk of venous thrombosis. The present study provides new insight into the links between environmental pollutants and venous thrombosis.

ABSTRACTBackground Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension.Methods and Results 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel–Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901.Conclusion Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function.

AbstractThe purpose of the article Pyoderma gangrenosum (PG) is an ulcerating neutrophilic dermatosis with an incidence of 3-10 patients per million. PG equally affects patients of both sexes and of any age. Of these patients, 50-75% are associated with auto-immune disease. The lower extremities are the most commonly affected body parts. Minor trauma to the skin may result in the development of new lesions. Patients complain of chronic, nonhealing ulcers with associated pain. Treatment starts with systemic or intralesional corticosteroids, however, no official treatment protocol currently exists. Recent success has been found with biologic agents such as TNF-a inhibitor, although the treatment efficacy in these reports is limited. As for the pregnant patient, the drug selection is difficult. In this report, we want to assess the efficiency of certolizumab in the pregnant patient.Results We report a case of a patient with PG, who responded well to certolizumab, 400 mg as a booster dose, followed by 200 mg biweekly for 8 weeks. The lesions gradually resolved and followed up for 5months without side effect. In addition, we reviewed the literature and compared the current treatment efficiency in the treatment of PG.Conclusion Certolizumab may be a promising therapeutic option for patients with severe PG.

A novel type of tubular structure with negative Poisson's ratio based on gyroid-type triply periodic minimal surfaces (TPMSs) is proposed in this study. This work is an attempt to design auxetic tubular structures based on TPMS. A series of auxetic tubular structures were designed and then fabricated using laser power bed fusion. Compressive behaviours of the fabricated auxetic tubular structures were investigated using experimental and numerical methods. To obtain optimal designs of tubular structures with controllable auxetic properties, the influence of several parameters were investigated comprehensively. Subsequently, several graded auxetic tubular structures were designed based on the parametric analysis and studied numerically. The mechanical properties of the tubular structures could be controlled effectively using the proposed approach. The proposed method can be used for guiding the design and optimisation of auxetic tubular structures, showing excellent potential for various applications such as biomedical devices, vehicle crashworthiness, and protective engineering.

Abstract Modules, toolboxes, and synthetic biology systems may be designed to address environmental bioremediation. However, weak and decentralized functional modules require complex control. To address this issue, an integrated system for toxicant detection and biodegradation, and subsequent suicide in chronological order without exogenous inducers is constructed. Salicylic acid, a typical pollutant in industrial wastewater, is selected as an example to demonstrate this design. Biosensors are optimized by regulating the expression of receptors and reporters to get 2‐fold sensitivity and 6‐fold maximum output. Several stationary phase promoters are compared, and promoter Pfic is chosen to express the degradation enzyme. Two concepts for suicide circuits are developed, with the toxin/antitoxin circuit showing potent lethality. The three modules are coupled in a stepwise manner. Detection and biodegradation, and suicide are sequentially completed with partial attenuation compared to pre‐integration, except for biodegradation, being improved by the replacements of ribosome binding site. Finally, a long‐term stability test reveals that the engineered strain maintained its function for ten generations. The study provides a novel concept for integrating and controlling functional modules that can accelerate the transition of synthetic biology from conceptual to practical applications.

Infectious bursal disease (IBD) classical virus strain (cIBDV) can cause morbidity and mortality in young chickens with severe long-term immunosuppression. However, since the emergence and widespread prevalence of very virulent strain (vvIBDV) in China from 1991, reports of cIBDV have become rare. A novel reassortant and recombinant strain GXYL211225 (genotype A1aB1a) with segment A originating from the classical strain (A1a) and segment B from the attenuated vaccine strain (B1a) was characterized in the study. Notably, segment A resulted from recombination between the cIBDV strains 150127-0.2 and Faragher52-70, expressing as a backbone from 150127-0.2, where a fragment located at the position of nucleotide (nt) 519-1 410 was replaced by the corresponding region of Faragher52-70. The infection of GXYL211225 caused mortality in SPF chicken embryos, despite lacking the critical amino acid (aa) residues 253H, 279 N and 284A associated with the cellular tropism, and induced significant cytopathic effect (CPE) on a wide range of cells, confirming its natural cell-adapted character. Furthermore, the challenge experiment of GXYL211225 was performed on the commercial Three-yellow chickens of 4-week-old, and with the vvIBDV HLJ-0504-like strain NN1172 and the novel variant (nv) IBDV strain QZ191002 as the comparison. All the challenged birds experienced reduced body-weight gain. QZ191002 infected birds showed no obvious clinical symptoms or mortality, while those of NN1172 and GXYL211225 showed typical IBD symptoms and resulted in 20% (2/10) and 10% (1/10) of mortality rates, respectively. At 7 days post-challenge (dpc), the damages of bursal of Fabricius (BF) varied among groups, with NN1172 causing the most severe lesions, followed by GXYL211225, and then QZ191002. It was also found that the pathogenicity was correlated positively with the viral load, aligning with the histopathological severity in BF. The study confirms the rapid and diverse evolution of the re-emerged classical strains in the field and emphasizes the need to monitor the changes of IBDV on both the genetic and pathogenic aspects for the effective control of the disease.

Global attention has been focused on organic UV filters due to their ubiquity and potential damage to aquatic environment, yet the effects of their life cycle exposure on fish reproduction remain unknown. In the present study, the influence of 2-phenylbenzimidazole-5-sulfonic acid (PBSA) exposure on the reproductive endocrine system of zebrafish was examined, from 6 hours post fertilization (hpf) until 150 days, at levels that near-environmentally relevant (0 to 20 μg/L). Our results showed that exposure to PBSA at 20 μg/L caused a slight decrease in the Gonadosomatic Index (GSI) of female zebrafish in the F0 generation. Furthermore, this exposure had a negatively effect on reproduction, accompanied by delayed oocyte maturation, reduced cumulative egg production and decreased fertilization rate. Additionally, offspring embryos displayed reduced egg diameter at 0.75 hpf, delayed cumulative hatching rate at 60 hpf, and increased deformities rate at 72 hpf, indicating an adverse transgenerational effect. Moreover, PBSA exposure was associated with decreased plasma levels of sex hormones of 17β-estradiol (E2) and 11-ketotestosterone (11-KT), as well as altered the transcriptional profiles of certain genes in the HPG (hypothalamic–pituitary–gonadal) and liver axis. Molecular docking (MD) simulations revealed that specific amino acid residues of PBSA interact with zebrafish estrogen receptors, confirming its xenoestrogenic properties. Therefore, exposure to PBSA during its life cycle can disturb fish reproduction through endocrine disruption, thus necessitating strict environmental regulations for the disposal of UV filters to protect ecological and public health.

Tumor subtyping based on its immune landscape may guide precision immunotherapy. The aims of this study were to identify immune subtypes of adult diffuse gliomas with RNA sequencing data, and to noninvasively predict this subtype using a biologically interpretable radiomic signature from MRI. A subtype discovery dataset (n = 210) from a public database and two radiogenomic datasets (n = 130 and 55, respectively) from two local hospitals were included. Brain tumor microenvironment‐specific signatures were constructed from RNA sequencing to identify the immune types. A radiomic signature was built from MRI to predict the identified immune subtypes. The pathways underlying the radiomic signature were identified to annotate their biological meanings. The reproducibility of the findings was verified externally in multicenter datasets. Three distinctive immune subtypes were identified, including an inflamed subtype marked by elevated hypoxia‐induced immunosuppression, a “cold” subtype that exhibited scarce immune infiltration with downregulated antigen presentation, and an intermediate subtype that showed medium immune infiltration. A 10‐feature radiomic signature was developed to predict immune subtypes, achieving an AUC of 0.924 in the validation dataset. The radiomic features correlated with biological functions underpinning immune suppression, which substantiated the hypothesis that molecular changes can be reflected by radiomic features. The immune subtypes, predictive radiomic signature, and radiomics‐correlated biological pathways were validated externally. Our data suggest that adult‐type diffuse gliomas harbor three distinctive immune subtypes that can be predicted by MRI radiomic features with clear biological significance. The immune subtypes, radiomic signature, and radiogenomic links can be replicated externally.

Mutations in the gene encoding PC1 cause ADPKD, a common genetic renal disease. Here, the authors show that expression of the C-terminal 200 amino acids of the large PC1 protein in mouse models of ADPKD suppresses cystic disease through an interaction with the mitochondrial enzyme NNT.

Abstract Purpose This study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer. Materials and methods Breast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively. Result From January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy. According to the AJCC 8th Edition standard, there were stage I in 26 patients, stage II in 22 patients, and stage III in 2 patients. A total of 14 patients received intensity-modulated proton therapy at a dose of 50 Gy in 25 fractions, followed by a 10 Gy 4 fractionated boost to the lumpectomy cavity, while 36 received 40.05 Gy in 15 fractions, simultaneous integrated boost (SIB) 48 Gy to the lumpectomy cavity. Median follow-up time for 40.05 Gy group was 35.6 months (15–43 months). Median follow-up time for 50 Gy group was 46.8 months (36–68 months). For acute toxicity, the grade 1 and 2 radiodermatitis in conventional-dose group were 35.7% and 57.1%, respectively. In hypofractionated dose group, the grade 1 and 2 radiodermatitis were 91.7% and 8.3%, respectively. The radiodermatitis is hypofractionneted dose better than conventional-dose significantly. Grade 1 radiation-induced esophagitis in conventional-dose group and hypofractionated dose group were 85.71% and 60%, respectively. For late toxicity, no patients developed radiation-induced pneumonitis and rib fracture in conventional-dose group. Three patients presented grade 1 pneumonitis; one patient presented graded 2 pneumonitides and two patients presented rib fracture in hypofractionated dose group. One presented hypothyroidism in hypofractionated dose group. All patients were satisfied with breast shape. The one- and two-year OS and DFS for conventional-dose group were 100 and 100; 100 and 92.9%, respectively. The one- and two-year OS and DFS for hypofractionated dose group were 100 and 100; 100 and 100%, respectively. Conclusion Proton radiation therapy can significantly reduce the normal tissue dose in breast cancer patients' hearts, lungs, and other organs. Hypofractionated proton therapy shortens the treatment course with mild radiation-related adverse effects, and has a better effect on addressing the acute adverse reactions than conventional proton radiotherapy.

Abstract Background Following viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain-specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-10−/−) model derived from the SvEv mouse, had evidence of increased Mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wild type. MMTV is endemic in several mouse strains as an endogenously encoded Betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut-associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10−/− model. Results Viral preparations extracted from IL-10−/− weanling stomachs revealed augmented MMTV load compared to the SvEv wild type. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4–97.3% identity with the mtv-1 endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTV sag gene cloned from IL-10−/− spleen encoded the MTV-9 superantigen that preferentially activates T-cell receptor Vβ-12 subsets, which were expanded in the IL-10−/− versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10−/− splenocytes with amplified interferon-γ production versus the SvEv wild type. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12-week treatment versus placebo. The combination antiretroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL-10−/− mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis. Conclusions This study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis. Video Abstract

[Objective] The differences in aggregate stability and infiltration characteristics of loess under different forest and grass vegetation restoration types were compared in order to provide a theoretical basis for the optimization of ecological restoration patterns in the Loess Plateau. [Methods] Abandoned land (C1, control), alfalfa land (C2), natural grassland (C3), mixed forest land of Pinus tabuliformis and Platycladus orientalis (L1), and mixed forest land of Robinia pseudoacacia and P. orientalis (L2) were used to investigate differences in aggregate stability and infiltration characteristics and their exogenous factors. Water-stable aggregate composition and saturated hydraulic conductivity were determined by the Savinov method and a single-ring two-ponding depth infiltrometer, respectively. Mean weight diameter (MWD), geometric mean diameter (GMD), fractal dimension (D), percentage of aggregate destruction (PAD), water-stable macroaggregate content (>0.25 mm, Mw), and saturated hydraulic conductivity sample (Ks) were used as evaluation indicators. [Results] ① In the 0—30 cm soil layer, C1 had the lowest GMD and MWD, and GMD and MWD in forest and grass vegetation restoration types followed the order of 〔L1 and C3〕>〔L2 and C2〕, respectively, whereas PAD and D showed the opposite order. ② In the 0—10 cm soil layer, L1 dominated the highest macroaggregate (>0.25 mm) content (47.24%), followed by C3 and L2, while C1 had the lowest content (24.00%). In the 10—30 cm soil layer, C3 dominated the highest macroaggregate (>0.25 mm) content (35.41% at 10—20 cm ; 27.96% at 20—30 cm), while L2 had the lowest content (11.46% at 10—20 cm; 8.00% at 20—30 cm). ③ The variation coefficients of topsoil infiltration characteristics for different restoration types ranged from 0.001 to 0.360. The Ks (0.307 cm/min) of L1 was the highest, while the Ks (0.044 cm/min) of C1 was the lowest. ④ Aggregate stability indicators (except PAD) and Ks were significantly correlated with soil organic carbon, porosity, and bulk density. [Conclusion] The restoration of forest and grass vegetation was beneficial for improving aggregate stability and infiltration performance. Compared with natural grassland, long-term forest restoration exhibited better aggregate stability and infiltration characteristics, but those characteristics were worse for short-term forest restoration than for natural grassland. Time accumulation should be emphasized when evaluating the effects of vegetation restoration.

Abstract End-stage renal disease (ESRD) results in hippocampal volume reduction, but the hippocampal subfields atrophy patterns cannot be identified. We explored the volumes and asymmetry of the hippocampal subfields and their relationships with memory function and biochemical changes. Hippocampal global and subfields volumes were derived from 33 ESRD patients and 46 healthy controls (HCs) from structural MRI. We compared the volume and asymmetric index of each subfield, with receiver operating characteristic curve analysis to evaluate the differentiation between ESRD and HCs. The relations of hippocampal subfield volumes with memory performance and biochemical data were investigated in ESRD group. ESRD patients had smaller hippocampal subfield volumes, mainly in the left CA1 body, left fimbria, right molecular layer head, right molecular layer body and right HATA. The right molecular layer body exhibited the highest accuracy for differentiating ESRD from HCs, with a sensitivity of 80.43% and specificity of 72.73%. Worse learning process (r = 0.414, p = 0.032), immediate recall (r = 0.396, p = 0.041) and delayed recall (r = 0.482, p = 0.011) was associated with left fimbria atrophy. The left fimbria volume was positively correlated with Hb (r = 0.388, p = 0.05); the left CA1 body volume was negatively correlated with Urea (r = − 0.469, p = 0.016). ESRD patients showed global and hippocampal subfields atrophy. Left fimbria atrophy was related to memory function. Anemia and Urea level may be associated with the atrophy of left fimbria and CA1 body, respectively.

This study assesses the enduring impact of combined school- and family-based interventions on reducing the consumption of sugar-sweetened beverages (SSBs) among schoolchildren in China. Two primary schools were assigned at random to either the Intervention Group or the Control Group, in Nanjing, eastern China. All students were in grade three and received an invitation to participate. In the first year, students in the Intervention Group received one-year intervention measures, including monthly monitoring, aiming to decrease the consumption of SSBs. Students in the Control Group only received regular monitoring without interventions. In the second year, both groups received only regular monitoring, without active interventions. A generalized estimating equations model (GEE) was used to assess the intervention effects. After two years, relative to the Control Group, the Intervention Group had a significantly improved knowledge of SSBs and an improved family environment with parents. In the Intervention Group, 477 students (97.3%) had adequate knowledge about SSBs, compared to 302 students (83.2%) in the Control Group (X2 = 52.708, p < 0.001). Two years later, the number of students who stated ‘my home always has SSBs’ in the Intervention Group (7.8%) was fewer than that in the Control Group (12.4%), which was a statistically significant finding (p < 0.05). One year later, both the frequency and the quantity of SSB consumption in the Intervention Group were less than those in the Control Group; such differences between the groups remained statistically significant for the quantity but not for the frequency of SSB consumption two years later. In the Intervention Group, the frequency of SSB consumption was significantly reduced by 1.0 times per week, compared to a reduction of 0.1 times per week in the Control Group in the first year (p < 0.05). In the second year, the frequency of SSB consumption was reduced by 0.8 times per week in the Intervention Group, compared to 0.5 times per week in the Control Group (p > 0.05). In the first year, the volume of SSB consumption was significantly reduced by 233 mL per week in the Intervention Group, compared to an increase of 107 mL per week in the Control Group (p < 0.05). In the second year, the volume of SSB consumption was reduced by 122 mL per week in the Intervention Group compared to an increase of 31 mL per week in the Control Group (p > 0.05). The combined school-based and family-based interventions had a positive effect on the students’ knowledge of SSBs and their family dynamics during the first and second year. Relative to the Control Group, the Intervention Group had a statistically significant reduction in SSB consumption after 1 year, but not after 2 years.

Surface cracks and joint deteriorations are typical premature failures of urban cement concrete pavement. However, traffic loads on the urban pavement are much lower than those on highways. Limited research has been conducted to investigate the causes of accelerated damage in urban cement concrete roads. To investigate the foundation issues that may cause the accelerated damage of urban cement concrete pavements, in this study, field evaluations were conducted to assess pavement foundation support and drainage conditions. Field visual inspections, Ground Penetrating Radar (GPR) survey, Dynamic Cone Penetrometer (DCP) test, and the Core-Hole Permeameter (CHP) test were performed. In urban residential areas with inadequate subgrade bearing capacity, cement concrete pavements are prone to early damage. Foundations with a higher content of coarse particles exhibit a higher CBR value, which can extend the service life of the pavement. The compaction of foundation materials near sewer pipelines and manholes is insufficient, leading to non-uniform support conditions. Moreover, the permeability of the foundation material can influence the service life of pavement surface structures. Foundation materials with fewer fine particles enhance drainage performance, contributing to a longer service life for PCC pavements. In areas with inadequate drainage, water accumulation reduces the bearing capacity of the foundation, thereby accelerating pavement deterioration. The poor bearing capacity and drainage conditions of the foundation lead to cavities between the surface layer and foundation material thus yielding stress concentrations on the pavement surface, which cause the formation of pavement surface cracks.

The atomic-level structure and electronic properties of monazite were investigated using a first-principles method based on density functional theory (DFT). First, the geometric structure of monazite was optimized, followed by calculations of its Mulliken population, electron density, and density of states, which were subsequently analyzed. The findings of this analysis suggest that monazite is highly susceptible to cleavage along the {100} plane during crushing and grinding. When SPA was utilized as the collector, the recovery rate of monazite was higher than that when LF-P8 was used. The zeta potential and adsorption energy results indicated that the zeta potential after SPA adsorption tended towards negativity, and the adsorption energy was smaller, indicating that SPA exhibited stronger adsorption performance. LF-P8 was stably adsorbed on the monazite (100) surface via mononuclear double coordination. SPA was stably adsorbed on the surface of monazite (100) via binuclear double coordination. The results of this study provide valuable insights into the adsorption of monazite by commonly used flotation collectors. These findings are of substantial importance for future endeavors in designing flotation collectors capable of achieving selective monazite flotation.

To overcome the difficulty of separating bastnaesite from fluorite through the flotation technique, the present study examined the suitability of sodium alginate (SA) as a depressant in the flotation process. The effect of SA on the flotation separation of bastnaesite and fluorite was evaluated using micro-flotation tests, zeta potential measurements, adsorption density measurements, Fourier infrared spectroscopy, and X-ray photoelectron spectroscopy. The micro-flotation results showed that SA exerted a strongly detrimental effect on fluorite flotation, while slightly affecting bastnaesite flotation. The surface chemistry results revealed that the -COO- and HO- functional groups in SA coordinated with Ca2+ on the fluorite surface, which induced hydrophilicity and hindered adsorption in the subsequent octylhydroxamic acid as a collector. However, the interaction of SA with the bastnaesite surface was marginal and did not affect the anchoring of the collector on the surface of bastnaesite. Based on these results, the present study proposes a possible model for the interaction of SA on the surfaces of the two minerals, laying a foundation for the flotation separation of bastnaesite from fluorite with SA as an environmentally benign depressant.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Currently, reinforced thin-walled irregular steel tube concrete frame structures have been applied in engineering, but there are few researches on the seismic performance of this type of structures after fire. The seismic performance of structures after fire is generally carried out based on rigid foundation conditions. Therefore, it is of certain engineering and theoretical value to study the seismic performance considering the SSI (soil–structure interaction) in this paper. ABAQUS is employed to establish the finite element models of the reinforced thin-walled irregular steel tube concrete frame structure considering the SSI after a fire. The paper analyzes the impact of different site conditions and fire durations on the structural natural vibration period, maximum acceleration, inter-story shear force, and maximum inter-story displacement angle. The results show that the consideration of the SSI increases the basic natural vibration period of the structure by 10–30%. The softer the soil and the longer the fire duration, the more significant the increase. For harder soil, lower seismic intensity, and shorter fire duration, the acceleration assigned to the structure and foundation after considering the SSI is smaller than the results assuming a rigid foundation. The change in inter-story shear force is mainly determined by the acceleration of the structure and foundation. The inter-story displacement angle increases when considering the SSI, and the increase is more significant with softer soil, larger seismic wave acceleration amplitude, and longer fire duration.

To resolve photons hungry for weak diffraction samples by the crystallographic method, a double-multilayer monochromator (DMM) was employed on an undulator beamline (BL17UM) at the Shanghai Synchrotron Radiation Facility (SSRF) to provide a focused sub-micron beam with high brightness for macromolecular crystallography experiments. High-quality crystallographic datasets from model protein crystal samples were collected and processed by an existing crystallographic program for structure solution and refinement. The data quality was compared with datasets from a normal silicon crystal monochromator to evaluate the bandwidth of the DMM effect on these crystallographic data. This experiment demonstrates that multilayer optics on an undulator beamline may play a valuable role in satisfying the demands of structure-related research, which requires novel methods.

Biomaterials with exceptional biocompatibility and bioactivity are now pushing the boundaries of bone tissue engineering. In this study, natural Arabic gum biopolymer incorporating titanium dioxide nanoparticles (NAG + TiO2NP) nanocomposite film was fabricated. The FTIR and XRD analysis show the presence of functional groups assigned to NAG biopolymers and highly crystalline anatase TiO2NP. Well dispersed TiO2NP can be seen from SEM micrograph suggesting good interaction between TiO2NP filler and NAG biopolymer matrix to enhance the mechanical characteristics of nanocomposite film. The NAG + TiO2NP nanocomposite film exhibited strong bioactivity to form bone-like apatite and promoted the proliferation of MG-63 cells attributed to their excellent biocompatibility and non-toxicity. The NAG + TiO2NP nanocomposite film also displays high antibacterial activity with (36.33 ± 1.53) mm and (27.00 ± 2.00) mm inhibition zone were recorded against Staphylococcus aureus and Escherichia coli. The findings indicate that the NAG + TiO2NP nanocomposite film, with its improved mechanical properties, high swelling capacity, biodegradability, and non-toxicity, shows promise as a viable option for bone tissue regeneration materials.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health.

Abstract The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

BRI1 EMS SUPPRESSOR1 (BES1) family members are crucial downstream regulators that positively mediate brassinosteroid signaling, playing vital roles in the regulation of plant stress responses and anther development in Arabidopsis. Importantly, the expression profiles of wheat (Triticum aestivum L.) BES1 genes have not been analyzed comprehensively and systematically in response to abiotic stress or during anther development. In this study, we identified 23 BES1-like genes in common wheat, which were unevenly distributed on 17 out of 21 wheat chromosomes. Phylogenetic analysis clustered the BES1 genes into four major clades; moreover, TaBES1-3A2, TaBES1-3B2 and TaBES1-3D2 belonged to the same clade as Arabidopsis BES1/BZR1 HOMOLOG3 (BEH3) and BEH4, which participate in anther development. The expression levels of 23 wheat BES1 genes were assessed using real-time quantitative PCR under various abiotic stress conditions (drought, salt, heat, and cold), and we found that most TaBES1-like genes were downregulated under abiotic stress, particularly during drought stress. We therefore used drought-tolerant and drought-sensitive wheat cultivars to explore TaBES1 expression patterns under drought stress. TaBES1-3B2 and TaBES1-3D2 expression was high in drought-tolerant cultivars but substantially repressed in drought-sensitive cultivars, while TaBES1-6D presented an opposite pattern. Among genes preferentially expressed in anthers, TaBES1-3B2 and TaBES1-3D2 expression was substantially downregulated in thermosensitive genic male-sterile wheat lines compared to common wheat cultivar under sterile conditions, while we detected no obvious differences under fertile conditions. This result suggests that TaBES1-3B2 and TaBES1-3D2 might not only play roles in regulating drought tolerance, but also participate in low temperature-induced male sterility.

Abstract Anti‐angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro‐angiogenic factors in the tumor microenvironment (TME) in response to anti‐angiogenic therapy, recruiting tumor‐associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti‐angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX‐PMI) co‐assembled by anti‐angiogenic nanomedicines (PCN‐Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs‐reprogramming polyTLR7/8a nanoregulators (p(Man‐IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN‐Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man‐IMDQ) NRs repolarize pro‐angiogenic M2‐type TAMs into anti‐angiogenic M1‐type TAMs via mannose‐binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1‐6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2‐subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti‐angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system‐based synergistic approach for tumor therapy.

Tiliroside, as a dietary flavonoid, has great potential in preventing or treating non-alcoholic fatty liver disease (NAFLD). However, research on tiliroside metabolism remains unclear, limiting its further utilization in healthcare. Herein, we explored the hepatoprotective effect of tiliroside and performed an UHPLC-Q-Exactive Orbitrap/MS-based set of experiments to identify metabolites and metabolic pathways of tiliroside in human hepatocytes. Results showed that tiliroside can exert antioxidant activity to protect against palmitic acid (PA)-induced oxidative injury in hepatocytes. Moreover, tiliroside was found to be considerably transformed through metabolism in human hepatocytes based on full MS and MS/MS analysis. Fifteen metabolites derived from the glucuronidation, sulfation, hydrolysis, and oxidation of tiliroside were identified. Glucuronidation and sulfation played key roles in tiliroside metabolism, accounting for approximately 32% and 20% of metabolism after 240 min incubation, respectively. The findings could provide a scientific basis for a more rational and effective application of tiliroside in healthcare.