RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2.

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3' splice site (ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3' ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

Identification and prediction of frailty among community-dwelling older Japanese adults based on Bayesian network analysis: a cross-sectional and longitudinal study.

BACKGROUND: Frailty is a multifactorial syndrome; through this study, we aimed to investigate the physiological, psychological, and social factors associated with frailty and frailty worsening in community-dwelling older adults. METHODS: We conducted a cross-sectional and longitudinal study using data from the "Community Empowerment and Well-Being and Healthy Long-term Care: Evidence from a Cohort Study (CEC)," which focuses on community dwellers aged 65 and above in Japan. The sample of the cross-sectional study was drawn from a CEC study conducted in 2014 with a total of 673 participants. After excluding those who were frail during the baseline assessment (2014) and at the 3-year follow-up (2017), the study included 373 participants. Frailty assessment was extracted from the Kihon Checklist, while social relationships were assessed using the Social Interaction Index (ISI). Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and their predictive abilities were tested. Factors associated with frailty status and worsening were identified through the Maximum-min Hillclimb algorithm applied to Bayesian networks (BNs). RESULTS: At baseline, 14.1% (95 out of 673) participants were frail, and 24.1% (90 out of 373) participants experienced frailty worsening at the 3-years follow up. LASSO regression identified key variables for frailty. For frailty identification (cross-sectional), the LASSO model's AUC was 0.943 (95%CI 0.913-0.974), indicating good discrimination, with Hosmer-Lemeshow (H-L) test p = 0.395. For frailty worsening (longitudinal), the LASSO model's AUC was 0.722 (95%CI 0.656-0.788), indicating moderate discrimination, with H-L test p = 0.26. The BNs found that age, multimorbidity, function status, and social relationships were parent nodes directly related to frailty. It revealed an 85% probability of frailty in individuals aged 75 or older with physical dysfunction, polypharmacy, and low ISI scores; however, if their social relationships and polypharmacy status improve, the probability reduces to 50.0%. In the longitudinal-level frailty worsening model, a 75% probability of frailty worsening in individuals aged 75 or older with declined physical function and ISI scores was noted; however, if physical function and ISI improve, the probability decreases to 25.0%. CONCLUSION: Frailty and its progression are prevalent among community-dwelling older adults and are influenced by various factors, including age, physical function, and social relationships. BNs facilitate the identification of interrelationships among these variables, quantify the influence of key factors. However, further research is required to validate the proposed model.

Research progress in tumor therapy of carrier-free nanodrug.

Carrier-free nanodrugs are a novel type of drug constructed by the self-assembly of drug molecules without carrier involvement. They have the characteristics of small particle size, easy penetration of various barriers, targeting tumors, and efficient release. In recent years, carrier-free nanodrugs have become a hot topic in tumor therapy as they solve the problems of low drug loading, poor biocompatibility, and low uptake efficiency of carrier nanodrugs. A series of recent studies have shown that carrier-free nanodrugs play a vital role in the treatment of various tumors, with similar or better effects than carrier nanodrugs. Based on the literature published in the past decades, this paper first summarizes the recent progress in the assembly modes of carrier-free nanodrugs, then describes common therapeutic modalities of carrier-free nanodrugs in tumor therapy, and finally depicts the existing challenges along with future trends of carrier-free nanodrugs. We hope that this review can guide the design and application of carrier-free nanodrugs in the future.

Efficacy and safety of platelet-rich plasma and hyaluronic acid combination therapy for knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate whether a combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) is more effective and safer than injection alone for treating KOA. MATERIALS AND METHODS: MEDLINE (PubMed), the Cochrane Library, EMBASE, and Web of Science databases were systematically searched for articles published until January 2024, and gray literature and bibliographic references were searched. All published randomized controlled trials (RCTs) compared pain, functional outcomes, and adverse events (AEs) associated with PRP + HA therapy vs. PRP or HA treatments. Two independent researchers extracted the pertinent data and evaluated the methodological quality following the PRISMA guidelines. The primary outcomes were pain, functional outcomes, and AEs. A fixed-effects model was used for data analysis in cases with low heterogeneity (P > 0.10 and I2 < 50%). Otherwise, a random effects model was used. RESULTS: Ten RCTs involving 943 patients were included in the analysis. The statistical findings did not differ between the treatment of PRP + HA and PRP alone, while a discernible enhancement in treatment efficacy was observed when compared to HA monotherapy: the visual analog scale scores at 1- (mean difference[MD], -1.00; 95% CI: -1.37 - -0.62; P < .001), 6- (MD, -1.87; 95% CI: -3.46 - -0.28; P = .02), 12-months (MD, -2.07; 95% CI: -3.77 - -0.38; P = .02), and the Western Ontario and McMaster Universities Arthritis Index total scores at 12-months (MD, -8.82; 95% CI: -14.48 - -3.16; P = .002). The incidence of adverse events was notably lower with PRP + HA than with HA alone (OR, 0.37; 95% CI: 0.19 - 0.69; P = .00) or PRP alone (OR, 0.51; 95% CI, 0.30 - 0.87; P = .01). CONCLUSIONS: PRP + HA therapy resulted in more pronounced pain and functional improvement in symptomatic KOA patients than HA treatments, and combination therapy may have higher clinical safety than PRP or HA monotherapy.

The relationship between competitive anxiety and athlete burnout in college athlete: the mediating roles of competence and autonomy : [Author].

BACKGROUND: In the cognitive-affective model of athlete burnout, anxiety is a key physiological response to stress that influences the development of burnout in athletes. Despite its importance, there has been little research on the relationship between competitive anxiety and athlete burnout, particularly regarding the mediating mechanisms. This study aimed to explore the relationship between competitive anxiety and athlete burnout, with a focus on the mediating role of general need satisfaction from self-determination theory. METHODS: The current study employed a cross-sectional design involving 618 college athletes (354 females, mean age 20.57 years), comprising 303 participants in individual sports and 315 in team sports. These participants completed the Sport Anxiety Scale-2 (SAS-2), the Athlete Burnout Questionnaire (ABQ), and the Basic Psychological Need Satisfaction Scale in General (BPNSS-G) online. Subsequently, correlation, regression, and mediation analyses were conducted using SPSS and JASP to examine the relationships between the variables. RESULTS: Regression results indicated that somatic anxiety (beta = 0.116, t = 2.21, p = 0.028) and concentration disruption (beta = 0.259, t = 5.35, p < 0.001) in competitive anxiety were positively correlated with athlete burnout. Worry in competitive anxiety was negatively correlated with competence (beta =-0.149, t=-2.70, p = 0.007) and autonomy (beta =-0.179, t=-3.25, p = 0.001) in needs satisfaction. Additionally, the regression results found that competence (beta =-0.178, t=-3.39, p = 0.001) and Autonomy (beta =-0.208, t=-4.17, p < 0.001) were negatively associated with athlete burnout. Mediation analyses revealed significant direct effects in the relationship between somatic anxiety (Effect = 0.116, p = 0.026) along with concentration disruption (Effect = 0.259, p < 0.001) and athlete burnout. In the indirect effect, worry (Effect = 0.071, p = 0.002) as well as concentration disruption (Effect = 0.082, p < 0.001) had significant effects in relation to athlete burnout, respectively. CONCLUSIONS: Overall, the current study found that somatic anxiety and concentration disruption in competitive anxiety are related to athlete burnout. Moreover, competence and autonomy in need satisfaction mediated the relationship between competitive anxiety (worry and concentration disruption) and athlete burnout. The findings of this study not only shed further light on the relationship between competitive anxiety and athlete burnout but also provide theoretical insights into the mediating mechanisms of this relationship.

RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway.

Aberrant alternative splicing is well-known to be closely associated with tumorigenesis of various cancers. However, the intricate mechanisms underlying breast cancer metastasis driven by deregulated splicing events remain largely unexplored. Here, we unveiled that RBM7 is decreased in lymph node and distant organ metastases of breast cancer as compared to primary lesions and low expression of RBM7 is correlated with the reduced disease-free survival of breast cancer patients. Breast cancer cells with RBM7 depletion exhibited an increased potential for lung metastasis compared to scramble control cells. The absence of RBM7 stimulated breast cancer cell migration, invasion, and angiogenesis. Mechanistically, RBM7 controlled the splicing switch of MFGE8, favoring the production of the predominant isoform of MFGE8, MFGE8-L. This resulted in the attenuation of STAT1 phosphorylation and alterations in cell adhesion molecules. MFGE8-L exerted an inhibitory effect on the migratory and invasive capability of breast cancer cells, while the truncated isoform MFGE8-S, which lack the second F5/8 type C domain had the opposite effect. In addition, RBM7 negatively regulates the NF-κB cascade and an NF-κB inhibitor could obstruct the increase in HUVEC tube formation caused by RBM7 silencing. Clinically, we noticed a positive correlation between RBM7 expression and MFGE8 exon7 inclusion in breast cancer tissues, providing new mechanistic insights for molecular-targeted therapy in combating breast cancer.

Effects of neonicotinoid residues on non-target soil animals: A case study of meta-analysis.

Neonicotinoids (NEOs) are currently the fastest-growing and most widely used insecticide class worldwide. Increasing evidence suggests that long-term NEO residues in the environment have toxic effects on non-target soil animals. However, few studies have conducted surveys on the effects of NEOs on soil animals, and only few have focused on global systematic reviews or meta-analysis to quantify the effects of NEOs on soil animals. Here, we present a meta-analysis of 2940 observations from 113 field and laboratory studies that investigated the effects of NEOs (at concentrations of 0.001-78,600.000 mg/kg) on different soil animals across five indicators (i.e., survival, growth, behavior, reproduction, and biochemical biomarkers). Furthermore, we quantify the effects of NEOs on different species of soil animals. Results show that NEOs inhibit the survival, growth rate, behavior, and reproduction of soil animals, and alter biochemical biomarkers. Both the survival rate and longevity of individuals decreased by 100 % with NEO residues. The mean values of juvenile survival, cocoon number, and egg hatchability were reduced by 97 %, 100 %, and 84 %, respectively. Both individual and cocoon weights were reduced by 82 %, while the growth rate decreased by 88 % with NEO residues. Our meta-analysis confirms that NEOs pose significant negative impacts on soil animals.

Surgical procedures and complications in placement of totally implantable venous access port in pediatric hemophilia patients: A retrospective analysis.

This retrospective study at Beijing Children's Hospital (2020-2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %-33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment.

Loss of RBM45 inhibits breast cancer progression by reducing the SUMOylation of IRF7 to promote IFNB1 transcription.

Type I interferons exhibit anti-proliferative and anti-cancer activities, but their detailed regulatory mechanisms in cancer have not been fully elucidated yet. RNA binding proteins are master orchestrators of gene regulation, which are closely related to tumor progression. Here we show that the upregulated RNA binding protein RBM45 correlates with poor prognosis in breast cancer. Depletion of RBM45 suppresses breast cancer progression both in cultured cells and xenograft mouse models. Mechanistically, RBM45 ablation inhibits breast cancer progression through regulating type I interferon signaling, particularly by elevating IFN-ß production. Importantly, RBM45 recruits TRIM28 to IRF7 and stimulates its SUMOylation, thereby repressing IFNB1 transcription. Loss of RBM45 reduced the SUMOylation of IRF7 by reducing the interaction between TRIM28 and IRF7 to promote IFNB1 transcription, leading to the inhibition of breast cancer progression. Taken together, our finding uncovers a vital role of RBM45 in modulating type I interferon signaling and cancer aggressive progression, implicating RBM45 as a potential therapeutic target in breast cancer.

Intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men in China: a national cross-sectional study.

Linking identified MPOX cases to care is essential for MPOX control. This study aims to investigate the intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men (MSM) in China. A cross-sectional online survey was conducted in early August 2023 in China. Respondents were recruited by community-based organizations (CBOs), collecting information on demographics, health status, behavioural and psychological characteristics. Univariate and multivariate logistic regression analyses were performed to examine the predictors of intentions to seek healthcare and self-isolate for MPOX within the MSM population. A total of 7725 participants were recruited, with a median age of 30 years. 92.21% of the participants would seek healthcare for MPOX-like symptoms, but only 52.50% intended to self-isolate if diagnosed. Intentions to seek healthcare were lower among those with MPOX-like symptoms in the past 3 months (standardized prevalence ratio (SPRs) = 0.82, 95% CI: 0.74-0.89) and the willingness to self-isolate was reduced among those diagnosed with MPOX in the past 3 months (SPRs = 0.65, 95% CI: 0.48-0.87). Participants free of sexually transmitted infections (STIs) and those aware of their HIV status were more likely to seek healthcare and self-isolate than those with STIs or unaware of their HIV status. Regular followers of MPOX information and those perceiving a low risk of infection were more inclined to take preventive measures. These findings highlight the need for targeted MPOX prevention strategies for high-risk groups and the importance of addressing barriers in infectious disease prevention response.

A simulation-driven prediction model for state of charge estimation of electric vehicle lithium battery.

Accurately predicting the state of charge (SOC) of lithium-ion batteries in electric vehicles is crucial for ensuring their stable operation. However, the component values related to SOC in the circuit typically require estimation through parameter identification. This paper proposes a three-stage method for estimating the SOC of lithium batteries in electric vehicles. Firstly, the parameters of the constructed second-order RC circuit are identified using the Forgetting Factor Recursive Least Squares (FFRLS) method. Secondly, an innovative approach is employed to construct a battery simulation model using modal-data fusion method. Finally, the predicted values of the simulation model are corrected using the unscented Kalman filter (UKF). Validation through datasets demonstrates the high precision of this method in parameter identification. Moreover, in the comparison of SOC prediction corrections with Particle Filter (PF), Extended Kalman Filter (EKF), and the proposed UKF on simulated prediction data and experimental test data. The proposed method achieves the lowest root mean square error (RMSE) of 0.0025 for simulation prediction data and 0.0186 for experimental test data. It also maintained its error within 5 % on actual data.

CD133 ligand-enhanced etoposide-liposome complex for targeted killing of lung cancer cells.

Lung cancer has a high incidence rate and a low cure rate, hence the urgent need for effective treatment methods. Current lung cancer drugs have several drawbacks, including low specificity, poor targeting, drug resistance, and irreversible damage to normal tissues. Therefore, there is a need to develop a safe and effective new drug that can target and kill tumor cells. In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand-modified etoposide-liposome complex (Lipo@ETP-CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor-killing effect. Our research results demonstrated that this nano-drug had efficient targeting and tumor-killing effects, indicating its potential for clinical application.

Longitudinal assessment of the relationship between frailty and social relationships among Japanese older adults: a random intercept cross-lagged panel model.

OBJECTIVES: This study aimed to explore the bidirectional association between frailty and social relationships in older adults while distinguishing between interpersonal and intrapersonal effects. METHODS: A prospective cohort study of community-dwelling older adults was conducted in Japan in three waves spanning six years with follow-ups in every three years. Random intercept cross-lagged panel model was used to explore temporal associations between frailty and social relationships. RESULTS: Data for 520 participants (mean age 73.02 [SD 6.38] years, 56.7% women) were analyzed. Across individuals, frailty was associated with social relationships (ß = -0.514, p < 0.001). At the interpersonal level, frailty was cross-sectionally associated with social relationships separately at T1(ß = -0.389, p < 0.01), T2 (ß = -0.343, p < 0.001) and T3 (ß = -0.273, p < 0.05). Moreover, social relationships were associated with subsequent increases in symptoms of frailty in all measurement waves (ß = -0.332, p < 0.001; ß = -0.169, p < 0.01) and vice versa (ß = -0.149, p < 0.05; ß = -0.292, p < 0.001). CONCLUSIONS: The results suggest that frailty was associated with lower levels of social relationships. Frailty improvement programs can be combined with interventions to enhance social relationships, which will be beneficial in preventing frailty. The results emphasize the importance of combining clinical treatments of frailty with interventions to improve social relationships.

Identification of splicing factors signature predicting prognosis risk and the mechanistic roles of novel oncogenes in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is the most frequent subtype of head and neck cancer, generally with a poor prognosis and limited therapeutic options due to its highly heterogeneous malignancy. In this study, we screened functional splicing regulatory RNA binding proteins (RBPs) that were closely related with the prognosis of HNSCC patients and showed significant expression differences between HNSCC tumors and normal tissues. Based on this finding, we chose six candidate genes (HNRNPC, ZCRB1, RBM12B, SF3A2, SF3B3, and SRSF11) to generate a prognostic prediction model and validated the accuracy of the prognostic model for predicting patient survival outcomes. We found that the risk score predicted by our model can serve as an independent prognostic predictor. Notably, HNSCC tumors showing higher expression of SF3B3, HNRNPC, or ZCRB1 possessed higher risk scores in the discovered prediction model. The investigation of the underlying mechanism validated that knockdown of SF3B3, HNRNPC, and ZCRB1 separately induced a substantial impairment of HNSCC cell survival. Conversely, overexpression of each of the three genes promoted tumor cellular proliferation. High throughput RNA sequencing analysis revealed that changes in the expression of SF3B3 and HNRNPC remarkably affected alternative splicing of genes related to cell cycle regulation, whereas the depletion of ZCRB1 contributed to aberrant splicing events involving in DNA damage response. In addition, the prognostic prediction model's risk score was demonstrated to be related with the immune infiltration score. Particularly, SF3B3 has a negative correlation with CD8A expression. Therefore, our findings provide promising prognosis predictors and potential therapeutic targets for better treatment efficacy of HNSCC.

Bayesian Optimization of Environmentally Sustainable Graphene Inks Produced by Wet Jet Milling.

Liquid phase exfoliation (LPE) of graphene is a potentially scalable method to produce conductive graphene inks for printed electronic applications. Among LPE methods, wet jet milling (WJM) is an emerging approach that uses high-speed, turbulent flow to exfoliate graphene nanoplatelets from graphite in a continuous flow manner. Unlike prior WJM work based on toxic, high-boiling-point solvents such as n-methyl-2-pyrollidone (NMP), this study uses the environmentally friendly solvent ethanol and the polymer stabilizer ethyl cellulose (EC). Bayesian optimization and iterative batch sampling are employed to guide the exploration of the experimental phase space (namely, concentrations of graphite and EC in ethanol) in order to identify the Pareto frontier that simultaneously optimizes three performance criteria (graphene yield, conversion rate, and film conductivity). This data-driven strategy identifies vastly different optimal WJM conditions compared to literature precedent, including an optimal loading of 15 wt% graphite in ethanol compared to 1 wt% graphite in NMP. These WJM conditions provide superlative graphene production rates of 3.2 g hr-1 with the resulting graphene nanoplatelets being suitable for screen-printed micro-supercapacitors. Finally, life cycle assessment reveals that ethanol-based WJM graphene exfoliation presents distinct environmental sustainability advantages for greenhouse gas emissions, fossil fuel consumption, and toxicity.

Porous ionic liquids for oxidative desulfurization influenced by electrostatic solvent effect.

Developing a highly efficient strategy for the stabilization of the solid-liquid interface is a persistent pursuit for researchers. Herein, porous ionic liquids based on UiO-66 (Zr) porous materials were synthesized and applied to the selective desulfurization catalysis, which integrates the permanent pores of porous solids with the exceptional properties of ionic liquids. Results show that porous ionic liquids possess high activity and selectivity for dibenzothiophene. Experimental analysis and density functional theory calculations revealed that the ionic liquids moiety served as an extractant to enrich dibenzothiophene into the porous ionic liquids phase through the π···π and CH···π interactions. Additionally, the electrostatic solvent effect in the porous ionic liquids contributes to the stabilization solid-liquid interface, which was favorable for UiO-66 moiety to catalytically activate hydrogen peroxide (H2O2) to generate ·OH radicals, and subsequently oxidized dibenzothiophene to the corresponding sulfone. It is hoped that the development of porous ionic liquids could pave a new route to the stabilization of the solid-liquid interface for catalytic oxidation.

RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.

Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti-metastatic drugs are still limited. Here it is reported that the RNA-binding protein RBMS1 is positively associated with increased lymph node metastasis in non-small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.

Automatic detection of mild cognitive impairment based on deep learning and radiomics of MR imaging.

Purpose: Early and rapid diagnosis of mild cognitive impairment (MCI) has important clinical value in improving the prognosis of Alzheimer's disease (AD). The hippocampus and parahippocampal gyrus play crucial roles in the occurrence of cognitive function decline. In this study, deep learning and radiomics techniques were used to automatically detect MCI from healthy controls (HCs). Method: This study included 115 MCI patients and 133 normal individuals with 3D-T1 weighted MR structural images from the ADNI database. The identification and segmentation of the hippocampus and parahippocampal gyrus were automatically performed with a VB-net, and radiomics features were extracted. Relief, Minimum Redundancy Maximum Correlation, Recursive Feature Elimination and the minimum absolute shrinkage and selection operator (LASSO) were used to reduce the dimensionality and select the optimal features. Five independent machine learning classifiers including Support Vector Machine (SVM), Random forest (RF), Logistic Regression (LR), Bagging Decision Tree (BDT), and Gaussian Process (GP) were trained on the training set, and validated on the testing set to detect the MCI. The Delong test was used to assess the performance of different models. Result: Our VB-net could automatically identify and segment the bilateral hippocampus and parahippocampal gyrus. After four steps of feature dimensionality reduction, the GP models based on combined features (11 features from the hippocampus, and 4 features from the parahippocampal gyrus) showed the best performance for the MCI and normal control subject discrimination. The AUC of the training set and test set were 0.954 (95% CI: 0.929-0.979) and 0.866 (95% CI: 0.757-0.976), respectively. Decision curve analysis showed that the clinical benefit of the line graph model was high. Conclusion: The GP classifier based on 15 radiomics features of bilateral hippocampal and parahippocampal gyrus could detect MCI from normal controls with high accuracy based on conventional MR images. Our fully automatic model could rapidly process the MRI data and give results in 1 minute, which provided important clinical value in assisted diagnosis.

The single metal atom (Ni, Pd, Pt) anchored on defective hexagonal boron nitride for oxidative desulfurization.

Single-atom catalysts (SACs) have attracted great attention for various chemical reactions because of their strong activity, high metal utilization ratio, and low cost. Here, by using the density functional theory (DFT) method, the stability of a single VIII-group metal atom (M = Ni, Pd, Pt) anchored on the defective hexagonal boron nitride (h-BN) sheet and its possible application in oxidative desulfurization (ODS) are investigated. Calculations show that the stability of the single M atom embedded in the h-BN surface with B and N vacancies is strikingly enhanced compared to that on the perfect h-BN surface. The catalytic activities of the defective h-BN-supported single metal atom are further studied by the activation of molecular oxygen and subsequent oxidation of dibenzothiophene (DBT). O2 is activated to the super-oxo state with large interaction energies on three M/VN surfaces. However, among the three M/VB surfaces, only Pt/VB performs efficient activation of O2. The oxidation of DBT proceeds in two steps; the rate-determining step is the initial step, in which activated O2 oxidizes DBT to produce sulfoxide. By comparing the energy barrier in the first reaction step, both Ni/VN and Pt/VB are revealed as promising candidates for the ODS reaction.

HNF4A as a potential target of PFOA and PFOS leading to hepatic steatosis: Integrated molecular docking, molecular dynamic and transcriptomic analyses.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are indeed among the most well known and extensively studied Per- and polyfluoroalkyl substances (PFASs), and increasing evidence confirm their effects on human health, especially liver steatosis. Nonetheless, the molecular mechanisms of their initiation of hepatic steatosis is still elusive. Therefore, potential targets of PFOA/PFOS must be explored to ameliorate its adverse consequences. This research aims to investigate the molecular mechanisms of PFOA and PFOS-induced liver steatosis, with emphasis on identifying a potential target that links these PFASs to liver steatosis. The potential target that causes PFOA and PFOS-induced liver steatosis have been explored and determined based on molecular docking, molecular dynamics (MD) simulation, and transcriptomics analysis. In silico results show that PFOA/PFOS can form a stable binding conformation with HNF4A, and PFOA/PFOS may interact with HNF4A to affect the downstream conduction mechanism. Transcriptome data from PFOA/PFOS-induced human stem cell spheres showed that HNF4A was inhibited, suggesting that PFOA/PFOS may constrain its function. PFOS mainly down-regulated genes related to cholesterol synthesis while PFOA mainly up-regulated genes related to fatty acid ß-oxidation. This study explored the toxicological mechanism of liver steatosis caused by PFOA/PFOS. These compounds might inhibit and down-regulate HNF4A, which is the molecular initiation events (MIE) that induces liver steatosis.