The evaluation of cytokines in predicting the organ injury of critically pediatric patients: a retrospective study.

Background: The current early warning model for organ damage in critically ill patients has certain limitations. Based on the pathological mechanism, the establishment of an early warning system for organ damage in critically ill children using cytokines profile has not been explored. The aim of this study is to explore the predicting value of cytokines in critically ill patients. Methods: There were 200 critically pediatric patients and 49 general patients between August 22, 2018 and April 28, 2023 from Children's Hospital of Soochow University enrolled in this study. The clinical information was retrospectively collected and analyzed. The cytokine profiles of these patients were detected by flow cytometry. Receiver operating characteristic (ROC) curves were plotted to determine the association between the cytokines and organ injury. Results: There were no statistically significant differences in gender, age and underlying disease between critically ill patients and general patients. The interleukin (IL)-6 (P<0.001), IL-10 (P<0.001), IL-17A (P=0.001), tumor necrosis factor-α (TNF-α) (P=0.02) and interferon-γ (IFN-γ) (P=0.02) level in the critically patients were significantly higher than those in the general patients. The results showed that the incidence of acute gastrointestinal injury (AGI) and acute kidney injury (AKI) in critically ill patients was 39% and 23.5%, respectively. Moreover, there were 4% and 3.5% patients with the occurrence of cardiac arrest and acute live injury. The IFN-γ level was increased in these patients with acute liver injury compared to those without these organ injuries, but reduced in the patients with AGI compared to those without. The patients with AKI showed a significant increase in IL-10 in contrast to those without. The IL-2, IL-4, IL-6, IL-10 and IL-17A were higher in patients with acute liver failure (ALF), but TNF-α was reduced, compared to those without. The IL-2, IL-4, IL-6 and IL-10 were significantly increased in the patients with cardiac arrest compared to those without. When IL-10 was higher than 279.45 pg/mL, the sensitivity and specificity for predicting cardiac arrest were 0.875 and 0.927, respectively. While the sensitivity and specificity of IL-6 (more than 1,425.6 pg/mL) were 0.625 and 0.844, respectively. However, no synergistic effect of IL-6 and IL-10 was observed for predicting cardiac arrest. Additionally, the IL-17A (more than 21.6 pg/mL) was a good predictor for the incidence of ALF (sensitivity =0.714, specificity =0.876). Conclusions: The cytokines profile was different between critically ill patients with organ injury and those without organ injury. The IL-6 and IL-10 levels were good predictors for cardiac arrest in critically ill patients. Additionally, higher IL-17A predicted the incidence of ALF of the critically ill patients.

Interfacial interactions of nanoscale zero-valent iron particles with clay minerals in the aquatic environments: Experimental and theoretical calculation study.

The environmental transport and fate of nanoscale zero-valent iron particles (nZVI) in soil and groundwater can be altered by their hetero-aggregation with clay mineral particles (CMP). This study examines the interactions between bare or carboxymethyl cellulose (CMC)-coated nZVI with typical CMP, specifically kaolinite and montmorillonite. Methods include co-settling experiments, aggregation kinetic studies, electron microscopy, Derjaguin-Landau-Verwey-Overbeek (DLVO) and extended DLVO (EDLVO) energy analysis, and density functional theory calculations, focusing on the pH dependency of these interactions. The EDLVO theory effectively described the interactions between nZVI and CMP in aquatic environments. Under acidic conditions (pH 3.5), the interfacial interaction between bare nZVI and kaolinite is regulated by van der Waals forces, while complexation, van der Waals forces, and electrostatic attraction govern the interaction of bare nZVI with montmorillonite, primarily depositing on the SiO face. In contrast, the positively charged AlO face and edge of CMP are the main deposition sites for CMC-coated nZVI through hydrogen bonding, van der Waals forces, and electrostatic attraction. At neutral (pH 6.5) and alkaline (pH 9.5) conditions, both bare and CMC-coated nZVI predominantly attach to the AlO face and edge, facilitated by complexation or hydrogen bonding, alongside van der Waals forces. The attachment of CMC-coated nZVI to CMP surfaces shows reversible aggregation or deposition due to the steric repulsion from the CMC coating. These findings hold significant implications for the environmental applications and risk of nZVI.

Smoking Susceptibility and Trends Among Nonsmoking Adolescents: An International Study.

OBJECTIVES: Smoking susceptibility is defined as a lack of firm decision against smoking, usually starts in the preparation and/or initiation stages of smoking behavior, and is a strong predictor of smoking experimentation during adolescence. However, the recent global prevalence and trends in smoking susceptibility among adolescents are not well documented. This study assessed global smoking susceptibility and secular trends among nonsmoking adolescents. METHODS: Smoking susceptibility was analyzed using the most recent data from the Global Youth Tobacco Survey from 129 countries, where the data from each country were drawn from at least 1 survey conducted at any time between 1999 and 2020. Moreover, data from 82 countries were used to assess the average annual rate of change (AARC) in smoking susceptibility over time. RESULTS: Smoking susceptibility among nonsmoking adolescents was 19.6%. A U-shaped relationship was observed between susceptibility and a country's economic level. Most countries showed no changes in susceptibility over time. Countries with a significant upward trend in susceptibility were primarily high-income and upper middle-income countries in the American region. At the World Health Organization regional level, susceptibility significantly decreased in the European region (AARC: -3.5%; 95% confidence interval, -5.8 to -0.8); however, it significantly increased in the American region (AARC: 2.2%; 95% confidence interval, 1.3-3.1). CONCLUSIONS: Smoking susceptibility remains a serious public health challenge among adolescents worldwide. More public health policies are needed to reduce susceptibility and to control its upward trend in the American region and high-income countries.

New materials-based on gelatin coordinated with zirconium or aluminum for ecological retanning.

Ecological retanning agent is an effective way to solve the pollution source of leather manufacturing industry. In this study, the gelatin from chrome-containing leather shavings in the leather industry was used to realize sustainable leather post-tanning. The gelatin hydrolysate (GH) coordinated with Zr4+ or Al3+ to prepare eco-friendly retanning agents GH-Zr and GH-Al. The successful coordination between GH and metal ions was characterized by FTIR and XPS. The retanning agents were characterized by FTIR curve-fitting and circular dichroism spectroscopy. The results showed that the conformation of the secondary structure of the polypeptide became ordered and stable after coordinating with the metal ions. The particle size and weight average molecular weight of the retanning agents were ~1700 nm and ~2100, respectively, measured by nanoparticle size analyzer and gel permeation chromatography (GPC). The retanning agents were applied to retanning of chrome tanned leather and glutaraldehyde tanned leather. The abundant free amino from retanning agents can consume the free formaldehyde. Meanwhile, retanning agents can effectively improve the multiple binding sites, resulting in favorable thickening rate (>110 %) and excellent dye and fatliquor absorption rate with ~99.91 % and ~93.18 %. Thus, this strategy can provide a viable choice for solid leather waste and sustainable development of the leather industry.

Effect of glutathione-assisted continuous renal replacement therapy in sepsis patients with acute renal injury.

This study explored the effect of glutathione assisted continuous renal replacement therapy (CRRT) on peripheral blood receptors in sepsis patients with acute kidney injury. A total of 196 sepsis patients with acute kidney injury were recruited to perform a retrospective cohort study, 98 patients treated with glutathione combined with CRRT were included as the combination group, and then 98 patients treated with CRRT alone were included as the control group during the same period. The outcome was changes in the levels of blood urea nitrogen (BUN), serum creatinine (Scr), peripheral blood receptors, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment (SOFA) before and after treatment. After treatment, the levels of BUN and Scr in both groups of patients were significantly lower than those before treatment, and the levels in the combination group were lower than those in the control group. After treatment, toll-like receptor (TLR) 4 and TLR2 levels in both groups of patients were lower than those before treatment, and the levels in the combination group were lower than those in the control group. After treatment, the APACHE II and SOFA scores of the two groups were lower than those before treatment, and the scores in the combination group were lower than those in the control group. Glutathione-assisted CRRT can improve the renal function of patients and reduce the immune inflammatory response of sepsis patients with acute kidney injury, which can be widely promoted in the clinic.

Unraveling EGFR-TKI resistance in lung cancer with high PD-L1 or TMB in EGFR-sensitive mutations.

BACKGROUND: Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms. METHODS: Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups. RESULTS: TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p < 0.001) and high TMB group (31% versus 13%, p < 0.05). Notably, PIK3CA and PTEN mutations emerged as the most important differentially mutated genes within the PI3K signaling pathway. CONCLUSIONS: Our findings reveal that the presence of PI3K signaling pathway mutations may be responsible for inducing primary resistance to EGFR-TKIs in NSCLC patients with EGFR-sensitive mutations along with high PD-L1 expression or high TMB. This finding is of great significance in guiding subsequent precision treatments in NSCLC.

Physiological Effects of Co-exposure to Ionizing Radiation and Noise within Occupational Exposure Limits.

ABSTRACT: Workers are frequently exposed to the occupational hazards of ionizing radiation and noise. Co-exposure to these hazards is not well understood in terms of their physiological effects. The aim of this study was to investigate the physiological effects of co-exposure to ionizing radiation and noise within the occupational limit. This study extracted the physical examination parameters of workers who met the screening criteria from the occupational health surveillance database. The workers were divided into three groups: the co-exposure (COE) group, the ionizing radiation exposure (ION) group, and the non-exposure (NON) group. The age and sex of the three groups were matched with a sample size ratio of 1:3:3. The physical examination parameters of the three groups of workers were compared. The results showed that there was no significant difference in blood pressure and blood biochemical parameters among the three groups. The COE group had higher levels of free triiodothyronine than the ION group, but there was no difference with the NON group. Moreover, the COE group had lower levels of free tetraiodothyronine than the ION group and the NON group. There was no significant difference in thyroid stimulating hormone, total triiodothyronine, and total tetraiodothyronine among the three groups. Additionally, the number of white blood cells of the COE group was lower than that of ION group and NON group. This study suggests that co-exposure to low-dose ionizing radiation and noise can cause alterations in thyroid hormone and peripheral white blood cells. These alterations are different from those observed after single exposure to low-dose ionizing radiation and require further research.

Targeted protein degrader development for cancer: advances, challenges, and opportunities.

Anticancer-targeted therapies inhibit various kinases implicated in cancer and have been used in clinical settings for decades. However, many cancer-related targets are proteins without catalytic activity and are difficult to target using traditional occupancy-driven inhibitors. Targeted protein degradation (TPD) is an emerging therapeutic modality that has expanded the druggable proteome for cancer treatment. With the entry of new-generation immunomodulatory drugs (IMiDs), selective estrogen receptor degraders (SERDs), and proteolysis-targeting chimera (PROTAC) drugs into clinical trials, the field of TPD has seen explosive growth in the past 10 years. Several challenges remain that need to be tackled to increase successful clinical translation of TPD drugs. We present an overview of the global landscape of clinical trials of TPD drugs over the past decade and summarize the clinical profiles of new-generation TPD drugs. In addition, we highlight the challenges and opportunities for the development of effective TPD drugs for future successful clinical translation.

Machine Learning Predicts Decompression Levels for Lumbar Spinal Stenosis Using Canal Radiomic Features from Computed Tomography Myelography.

BACKGROUND: The accurate preoperative identification of decompression levels is crucial for the success of surgery in patients with multi-level lumbar spinal stenosis (LSS). The objective of this study was to develop machine learning (ML) classifiers that can predict decompression levels using computed tomography myelography (CTM) data from LSS patients. METHODS: A total of 1095 lumbar levels from 219 patients were included in this study. The bony spinal canal in CTM images was manually delineated, and radiomic features were extracted. The extracted data were randomly divided into training and testing datasets (8:2). Six feature selection methods combined with 12 ML algorithms were employed, resulting in a total of 72 ML classifiers. The main evaluation indicator for all classifiers was the area under the curve of the receiver operating characteristic (ROC-AUC), with the precision-recall AUC (PR-AUC) serving as the secondary indicator. The prediction outcome of ML classifiers was decompression level or not. RESULTS: The embedding linear support vector (embeddingLSVC) was the optimal feature selection method. The feature importance analysis revealed the top 5 important features of the 15 radiomic predictors, which included 2 texture features, 2 first-order intensity features, and 1 shape feature. Except for shape features, these features might be eye-discernible but hardly quantified. The top two ML classifiers were embeddingLSVC combined with support vector machine (EmbeddingLSVC_SVM) and embeddingLSVC combined with gradient boosting (EmbeddingLSVC_GradientBoost). These classifiers achieved ROC-AUCs over 0.90 and PR-AUCs over 0.80 in independent testing among the 72 classifiers. Further comparisons indicated that EmbeddingLSVC_SVM appeared to be the optimal classifier, demonstrating superior discrimination ability, slight advantages in the Brier scores on the calibration curve, and Net benefits on the Decision Curve Analysis. CONCLUSIONS: ML successfully extracted valuable and interpretable radiomic features from the spinal canal using CTM images, and accurately predicted decompression levels for LSS patients. The EmbeddingLSVC_SVM classifier has the potential to assist surgical decision making in clinical practice, as it showed high discrimination, advantageous calibration, and competitive utility in selecting decompression levels in LSS patients using canal radiomic features from CTM.

Immobile Iron-Rich Particles Promote Arsenic Retention and Regulate Arsenic Biotransformation in Treatment Wetlands.

Remediation of arsenic (As)-contaminated wastewater by treatment wetlands (TWs) remains a technological challenge due to the low As adsorption capacity of wetland substrates and the release of adsorbed As to pore water. This study investigated the feasibility of using immobile iron-rich particles (IIRP) to promote As retention and to regulate As biotransformation in TWs. Iron-rich particles prepared were immobilized in the interspace of a gravel substrate. TWs with IIRP amendment (IIRP-TWs) achieved a stable As removal efficiency of 63 ± 4% over 300 days, while no As removal or release was observed in TWs without IIRP after 180 days of continuous operation. IIRP amendment provided additional adsorption sites and increased the stability of adsorbed As due to the strong binding affinity between As and Fe oxides. Microbially mediated As(III) oxidation was intensified by iron-rich particles in the anaerobic bottom layer of IIRP-TWs. Myxococcus and Fimbriimonadaceae were identified as As(III) oxidizers. Further, metagenomic binning suggested that these two bacterial taxa may have the capability for anaerobic As(III) oxidation. Overall, this study demonstrated that abiotic and biotic effects of IIRP contribute to As retention in TWs and provided insights into the role of IIRP for the remediation of As contamination.

Machine Learning Predict Survivals of Spinal and Pelvic Ewing's Sarcoma with the SEER Database.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: This study aimed to develop survival prediction models for spinal Ewing's sarcoma (EWS) based on machine learning (ML). METHODS: We extracted the SEER registry's clinical data of EWS diagnosed between 1975 and 2016. Three feature selection methods extracted clinical features. Four ML algorithms (Cox, random survival forest (RSF), CoxBoost, DeepCox) were trained to predict the overall survival (OS) and cancer-specific survival (CSS) of spinal EWS. The concordance index (C-index), integrated Brier score (IBS) and mean area under the curves (AUC) were used to assess the prediction performance of different ML models. The top initial ML models with best performance from each evaluation index (C-index, IBS and mean AUC) were finally stacked to ensemble models which were compared with the traditional TNM stage model by 3-/5-/10-year Receiver Operating Characteristic (ROC) curves and Decision Curve Analysis (DCA). RESULTS: A total of 741 patients with spinal EWS were identified. C-index, IBS and mean AUC for the final ensemble ML model in predicting OS were .693/0.158/0.829 during independent testing, while .719/0.171/0.819 in predicting CSS. The ensemble ML model also achieved an AUC of .705/0.747/0.851 for predicting 3-/5-/10-year OS during independent testing, while .734/0.779/0.830 for predicting 3-/5-/10-year CSS, both of which outperformed the traditional TNM stage. DCA curves also showed the advantages of the ensemble models over the traditional TNM stage. CONCLUSION: ML was an effective and promising technique in predicting survival of spinal EWS, and the ensemble models were superior to the traditional TNM stage model.

Sex and macroeconomic differences and trends in early attempts at cigarette smoking among adolescents: findings from 147 countries.

BACKGROUND: Most tobacco users initiate smoking during adolescence. Little is known about the global prevalence and trends in early cigarette smoking among adolescents. This study aimed to evaluate the prevalence of early attempts at cigarette smoking and its change trends among young adolescents. METHODS: We used data from the Global Youth Tobacco Surveys on adolescents aged 12-16 years, comprising 456,634 participants from 147 countries between 2006 and 2018, to estimate the prevalence of early attempts at cigarette smoking and age distribution at attempt by sex, country income, purchasing power parity (PPP) per capita, and WHO region. We assessed the average annual rate of reduction (AARR) in the prevalence of attempts at cigarette smoking before 12 years of age in 70 countries that had data from three or more surveys completed between 1999 and 2018. RESULTS: The average prevalence of early attempts at cigarette smoking was 12.2% (95% CI: 10.9-13.5) for boys and 6.7% (95% CI: 5.8-7.6) for girls, with the highest prevalence of 17.4% for boys and 10.7% for girls in the European region. Along with the growth of the national economy, the prevalence of early attempts at cigarette smoking gradually increased in both sexes. A total of 22.9% and 30% of countries had a negative change in AARR for boys and for girls, respectively. The countries with an upward prevalence were mainly located in the Eastern Mediterranean, Southeast Asia, and African regions. The age distribution at first cigarette smoked did not differ substantially between sexes. Notably, the age at first cigarette smoked of 10.7 years for girls was significantly earlier than that of 11.8 years for boys in low-income countries. Among cigarette-smoking adolescents, the average percentage of girls reporting smoking their first cigarette at an age <12 years was 55.7% in Q1 for PPP quintiles, 46.5% in Q2, 40.3% in Q3, 38.4% in Q4, and 34.6% in Q5, and the corresponding prevalence for boys was 46.0% in Q1, 42.8% in Q2, 42.9% in Q3, 43.5% in Q4, and 41.1% in Q5. CONCLUSIONS: The global prevalence of early attempts at cigarette smoking among adolescents was substantial, with differences by sex and macroeconomic situation, and our findings stress that interventions and policies targeting the first smoking experience are required to prevent the initiation of tobacco use among early adolescents, especially girls in low-income countries.

Accuracy and reliability analysis of a machine learning based segmentation tool for intertrochanteric femoral fracture CT.

Introduction: Three-dimensional (3D) reconstruction of fracture fragments on hip Computed tomography (CT) may benefit the injury detail evaluation and preoperative planning of the intertrochanteric femoral fracture (IFF). Manually segmentation of bony structures was tedious and time-consuming. The purpose of this study was to propose an artificial intelligence (AI) segmentation tool to achieve semantic segmentation and precise reconstruction of fracture fragments of IFF on hip CTs. Materials and Methods: A total of 50 labeled CT cases were manually segmented with Slicer 4.11.0. The ratio of training, validation and testing of the 50 labeled dataset was 33:10:7. A simplified V-Net architecture was adopted to build the AI tool named as IFFCT for automatic segmentation of fracture fragments. The Dice score, precision and sensitivity were computed to assess the segmentation performance of IFFCT. The 2D masks of 80 unlabeled CTs segmented by AI tool and human was further assessed to validate the segmentation accuracy. The femoral head diameter (FHD) was measured on 3D models to validate the reliability of 3D reconstruction. Results: The average Dice score of IFFCT in the local test dataset for "proximal femur", "fragment" and "distal femur" were 91.62%, 80.42% and 87.05%, respectively. IFFCT showed similar segmentation performance in cross-dataset, and was comparable to that of human expert in human-computer competition with significantly reduced segmentation time (p < 0.01). Significant differences were observed between 2D masks generated from semantic segmentation and conventional threshold-based segmentation (p < 0.01). The average FHD in the automatic segmentation group was 47.5 ± 4.1 mm (41.29∼56.59 mm), and the average FHD in the manual segmentation group was 45.9 ± 6.1 mm (40.34∼64.93 mm). The mean absolute error of FHDs in the two groups were 3.38 mm and 3.52 mm, respectively. No significant differences of FHD measurements were observed between the two groups (p > 0.05). All ICCs were greater than 0.8. Conclusion: The proposed AI segmentation tool could effectively segment the bony structures from IFF CTs with comparable performance of human experts. The 2D masks and 3D models generated from automatic segmentation were effective and reliable, which could benefit the injury detail evaluation and preoperative planning of IFFs.

Automated Breast Volume Scanner (ABVS)-Based Radiomic Nomogram: A Potential Tool for Reducing Unnecessary Biopsies of BI-RADS 4 Lesions.

Improving the assessment of breast imaging reporting and data system (BI-RADS) 4 lesions and reducing unnecessary biopsies are urgent clinical issues. In this prospective study, a radiomic nomogram based on the automated breast volume scanner (ABVS) was constructed to identify benign and malignant BI-RADS 4 lesions and evaluate its value in reducing unnecessary biopsies. A total of 223 histologically confirmed BI-RADS 4 lesions were enrolled and assigned to the training and validation cohorts. A radiomic score was generated from the axial, sagittal, and coronal ABVS images. Combining the radiomic score and clinical-ultrasound factors, a radiomic nomogram was developed by multivariate logistic regression analysis. The nomogram integrating the radiomic score, lesion size, and BI-RADS 4 subcategories showed good discrimination between malignant and benign BI-RADS 4 lesions in the training (AUC, 0.959) and validation (AUC, 0.925) cohorts. Moreover, 42.5% of unnecessary biopsies would be reduced by using the nomogram, but nine (4%) malignant BI-RADS 4 lesions were unfortunately missed, of which 4A (77.8%) and small-sized (<10 mm) lesions (66.7%) accounted for the majority. The ABVS radiomics nomogram may be a potential tool to reduce unnecessary biopsies of BI-RADS 4 lesions, but its ability to detect small BI-RADS 4A lesions needs to be improved.

Research topics and hotspot trends of lumbar spondylolisthesis: A text-mining study with machine learning.

Objectives: The study aimed to conduct a bibliometric analysis of publications concerning lumbar spondylolisthesis, as well as summarize its research topics and hotspot trends with machine-learning based text mining. Methods: The data were extracted from the Web of Science Core Collection (WoSCC) database and then analyzed in Rstudio1.3.1 and CiteSpace5.8. Annual publication production and the top-20 productive authors over time were obtained. Additionally, top-20 productive journals and top-20 influential journals were compared by spine-subspecialty or not. Similarly, top-20 productive countries/regions and top-20 influential countries/regions were compared by they were developed countries/regions or not. The collaborative relationship among countries and institutions were presented. The main topics of lumbar spondylolisthesis were classified by Latent Dirichlet allocation (LDA) analysis, and the hotspot trends were indicated by keywords with strongest citation bursts. Results: Up to 2021, a total number of 4,245 articles concerning lumbar spondylolisthesis were finally included for bibliometric analysis. Spine-subspecialty journals were found to be dominant in the productivity and the impact of the field, and SPINE, EUROPEAN SPINE JOURNAL and JOURNAL OF NEUROSURGERY-SPINE were the top-3 productive and the top-3 influential journals in this field. USA, Japan and China have contributed to over half of the publication productivity, but European countries seemed to publish more influential articles. It seemed that developed countries/regions tended to produce more articles and more influential articles, and international collaborations mainly occurred among USA, Europe and eastern Asia. Publications concerning surgical management was the major topic, followed by radiographic assessment and epidemiology for this field. Surgical management especially minimally invasive technique for lumbar spondylolisthesis were the recent hotspots over the past 5 years. Conclusions: The study successfully summarized the productivity and impact of different entities, which should benefit the journal selection and pursuit of international collaboration for researcher who were interested in the field of lumbar spondylolisthesis. Additionally, the current study may encourage more researchers joining in the field and somewhat inform their research direction in the future.

Crash landing of Vibrio cholerae by MSHA pili-assisted braking and anchoring in a viscoelastic environment.

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment of Vibrio cholerae, the first step of V. cholerae colonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labeling method with single-cell tracking techniques, we quantitatively characterized the landing of V. cholerae by directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which includes three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics of V. cholerae under viscoelastic conditions, which can provide insights into ways to better control V. cholerae infections in a real mucus-like environment.

Synergetic integration of thermal conductivity and flame resistance in nacre-like nanocellulose composites.

Highly thermally conductive and flame resistant nanocellulose-based composites can synchronously achieve efficient thermal dissipation and low fire hazards of electronic devices, which shows great promise in next-generation green and flexible electronics. However, it has long been intractable to optimize the high thermal conductivity (TC) and flame resistance simultaneously. Herein, synergetic integration of high TC and flame resistance in nacre-like nanocellulose composites has been successfully achieved by the vacuum-assisted filtration of cellulose nanofibers (CNFs) and functionalized boron nitride nanosheets (BNNS-p-APP). Benefiting from the highly oriented hierarchical microstructure, strong hydrogen-bonding interaction, and successful immobilization of ammonium polyphosphate (APP), the as-obtained CNFs/BNNS-p-APP composite film achieves a high in-plane TC of 9.1 W m-1 K-1 and outstanding flame resistance. Meantime, this eco-friendly nanocellulose-based composite also exhibits remarkable flexibility, folding endurance, and mechanical robustness, robustness, which may open up a new opportunity for the thermal management of flexible electronics.

Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3ß signaling axis in hepatocellular carcinoma cells.

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3ß (GSK-3ß) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3ß was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3ß and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3ß signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.

The association of eating behaviors with blood pressure levels in college students: a cross-sectional study.

BACKGROUNDS: The present study aimed to investigate the relationship between eating habits and blood pressure levels in college students in order to provide more insights into the prevention and control of hypertension. METHODS: A self-administered questionnaire was distributed to first-year college students. The demographic characteristics, eating behaviors, smoking and drinking status, and physical activity of 3,324 eligible respondents were analyzed. Multivariate logistics regression model was used to analyze the association of eating behaviors with blood pressure levels. RESULTS: The study participants had a mean (SD) age of 18.51 (1.00) years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were 114.08 and 70.92 mmHg, respectively. The overall prevalence of hypertension was 7.2%; and the prevalence among males and females was 12.9% and 3.2%, respectively. Multivariate logistic regression results confirmed that students' taste preference, desserts, and late-night snacks were associated with hypertension. Students who ate spicy food had a lower risk of high blood pressure (OR =0.642, P=0.028); as was having dessert 3-6 times a week (OR =0.702, P=0.037), while those who ate late-night snacks on 6-7 days of the week had a higher risk for hypertension (OR =2.093, P=0.013). CONCLUSIONS: More targeted interventions should be taken to improve students' eating habits and control their blood pressure.