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Mechanism of Radix Bupleuri and Hedysarum Multijugum Maxim drug pairs on liver fibrosis based on network pharmacology, bioinformatics and molecular dynamics simulation
A number of studies demonstrate the therapeutic effectiveness of Radix Bupleuri (RB) and Hedysarum Multijugum Maxim (HMM) in treating liver fibrosis, but the exact molecular mechanisms remain unclear. This study aims to explore the mechanism of RB-HMM drug pairs in treating liver fibrosis by using network pharmacology, bioinformatics, molecular docking, molecular dynamics simulation technology and in vitro experiments. Totally, 155 intersection targets between RB-HMM and liver fibrosis were identified. In the protein-protein interaction (PPI) network, the top 10 hub targets with the highest node connection values were TNF, IL-6, AKT1, EGFR, HIF1A, PPARG, CASP3, SRC, MMP9 and HSP90AA1. GO functional and KEGG pathway enrichment analysis involved 335 biological processes, 39 cellular components, 78 molecular functions, and 139 signaling pathways. The bioinformatics analysis indicated that TNF, IL-6, PPARG and MMP9 were promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver fibrosis. Moreover, the molecular docking and molecular dynamic simulation of 50 ns well complemented the binding affinity and strong stability between the three common compounds MOL000098 (quercetin), MOL000354 (isorhamnetin) and MOL000422 (kaempferol) and four final hub targets (TNF, IL-6, PPARG and MMP9). Calculation of binding free energy and decomposition free energy using MM_PBSA and MM_GBSA also validated the strong binding affinity and stability of 12 systems. MOL000098 (quercetin) was selected via MTT assay and western blot assay verified MOL000098 (quercetin) treatments remarkably decreased the protein levels of TNF and IL-6 in TGFβ stimulated LX2 cells. In conclusion, RB-HMM drug pairs can affect the progression of liver fibrosis through multiple components, multiple targets and multiple pathways, and treat liver fibrosis possibly through anti-inflammatory and affecting cell apoptosis.
Author Correction: Contemporary survival outcomes of congenital systemic-to-pulmonary shunt in children with borderline pulmonary vascular resistant index compared to Eisenmenger syndrome
Association between lipid accumulation product and the risk of colon cancer in adults: A population-based study
Background The purpose of this study was to look into any potential connections between the occurrence of colon cancer and the condition of the body of lipid accumulation product (LAP) index. Methods Using data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES), we performed a cross-sectional analysis with 24,592 individuals. Utilizing multivariate logistic regression modelling, the relationship between LAP levels and colon cancer risk was investigated. Subgroup analysis, trend test, interaction test, and stratified smoothed curve were also carried out. Results LAP levels and colon cancer risk were positively correlated after controlling for potential covariates (OR = 10.56, 95% CI: 2.40–46.53), the findings of trend tests are statistically significant. In particular groups, subgroup analysis revealed a positive connection between LAP levels and the risk of colon cancer. The association between LAP levels and colon cancer risk was shown to be M-shaped in the group under 60 years old, inverted V-shaped in the female and no-diabetes groups, and inverted L-shaped in the smoking and no-hypertensive groups, according to stratified smoothed curve fitting. Conclusions According to our findings, there is a strong correlation between LAP levels and the risk of colon cancer.
Squared diffusion-weighted imaging for improving the detection of clinically significant prostate cancer
Abstract Aim of this study was to proof the concept of optimizing the contrast between prostate cancer (PC) and healthy tissue by DWI post-processing using a quadrature method. DWI post-processing was performed on 30 patients (median age 67 years, prostate specific antigen 8.0 ng/ml) with PC and clear MRI findings (PI-RADS 4 and 5). Multiparametric MRI was performed at 3 Tesla. A multi-shot readout segmentation (rs-EPI) plus zoomed single-shot imaging (z-EPI) sequence was used in 15 patients (group 1) and a single-shot echo-planar imaging (ss-EPI) plus rs-EPI sequence in 15 patients (group 2). B-value images (b1000 and b1800/2000) were squared and then evaluated objectively software-based and subjectively using a 5-point. The squared DWI technique showed a significantly higher contrast ratio (CR) for ss-EPI b1800 (p < 0.001), rs-EPI b1000 (p < 0.001), rs-EPI b1800 (p < 0.001), z-EPI b1000 (p = 0.008) and for z-EPI b2000 (p < 0.001). After post-processing, a significant improvement in the subjective assessment of image quality was observed for rs-EPI b1000 (p < 0.001), rs-EPI b1800 (p < 0.001) and z-EPI b1000 (p < 0.001). The application of the square post-processing to DWI results in a significant improvement in the CR between PC and healthy tissue, especially at high b-values of ss-EPI or re-EPI. This method may help to improve the detection and differentiation of PC lesions.
Chemigenetic Ca2+ indicators report elevated Ca2+ levels in endothelial Weibel-Palade bodies
Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 µm and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing/processing after translation into the ER. ER, Golgi and WPB themselves provide a unique milieu for the maturation of VWF, which at the level of the Golgi consists of a low pH and elevated Ca2+ concentrations. WPB are also characterized by low luminal pH, but their Ca2+ content has not been addressed so far. Here, we employed a chemigenetic approach to circumvent the problems of Ca2+ imaging in an acidic environment and show that WPB indeed also harbor elevated Ca2+ concentrations. We also show that depletion of the Golgi resident Ca2+ pump ATP2C1 resulted in only a minor decrease of luminal Ca2+ in WPB suggesting additional mechanisms for Ca2+ uptake into the organelle.
Simulation analysis of radiometer effect and outgassing based on molecular particle source perturbation
Optimal aspiration pressure of suction pump for oocyte retrieval in infertile patients undergoing in vitro fertilization
Background The oocyte retrieval is a critical step in assisted reproductive technologies, including in vitro fertilization and fertility preservation. Despite evolving techniques, the optimal aspiration pressure during retrieval remains debatable, with limited in vivo human studies. Existing studies, primarily in vitro and on animals, suggest that inappropriate aspiration pressures can impair oocyte quality. This study aims to compares the effects of two different aspiration pressures, 120mmHg and 150mmHg, on oocyte recovery, damage, and subsequent embryo development and pregnancy outcomes in infertile women undergoing transvaginal ultrasound-guided oocyte retrieval. Methods and findings This retrospective study analyzed data from 891 women at Seoul National University Hospital between May 2018 and August 2023. A total of 400 cycles were included, with 202 at 120 mmHg and 198 at 150 mmHg aspiration pressures. The primary outcomes were the number of retrieved, matured, fractured oocytes, embryos, and good-grade embryos. Pregnancy outcomes were evaluated by comparing the clinical pregnancy rates and live birth rates. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship between aspiration pressure, clinical pregnancy, and live birth rates. There was statistically significant difference in the number of retrieved oocytes and mature oocytes between the 120 mmHg group and the 150 mmHg group (6.3±5.2 vs. 7.7±6.7, p = 0.018; 4.4±3.7 vs. 5.6±5.3, p = 0.011). The number of embryos and good grade embryos also differed significantly (3.3±3.1 vs. 4.2±3.9, p = 0.011; 1.0±1.6 vs. 1.5±2.6, p = 0.031). However, there were no significant differences in clinical pregnancy and live birth rates between the two groups in multivariate logistic regression analysis (adjusted OR = 0.725, p = 0.519; adjusted OR = 0.370, p = 0.170). Conclusions Increasing the aspiration pressure to 150mmHg led to a higher yield of oocytes and embryos than 120mmHg, without any negative impact on oocyte quality or live birth rates. These findings provide valuable insights for clinical decision-making in infertility treatments, suggesting that 150mmHg may be a more effective pressure for oocyte retrieval in in vitro fertilization and embryo transfer.
Dual-task-related gait patterns as possible marker of precocious and subclinical cognitive alterations in Parkinson disease
Classification of CT scan and X-ray dataset based on deep learning and particle swarm optimization
In 2019, the novel coronavirus swept the world, exposing the monitoring and early warning problems of the medical system. Computer-aided diagnosis models based on deep learning have good universality and can well alleviate these problems. However, traditional image processing methods may lead to high false positive rates, which is unacceptable in disease monitoring and early warning. This paper proposes a low false positive rate disease detection method based on COVID-19 lung images and establishes a two-stage optimization model. In the first stage, the model is trained using classical gradient descent, and relevant features are extracted; in the second stage, an objective function that minimizes the false positive rate is constructed to obtain a network model with high accuracy and low false positive rate. Therefore, the proposed method has the potential to effectively classify medical images. The proposed model was verified using a public COVID-19 radiology dataset and a public COVID-19 lung CT scan dataset. The results show that the model has made significant progress, with the false positive rate reduced to 11.3% and 7.5%, and the area under the ROC curve increased to 92.8% and 97.01%.
Utilizing large-scale human mobility data to identify determinants of physical activity
Intellectual capital, digital transformation and firms’ financial performance: Evidence from ecological protection and environmental governance industry in China
As the pace of enterprise digital transformation accelerates, intellectual capital (IC) has become a core driving force of gaining market competitive advantages and enhancing value creation capabilities. The paper aims to investigate the impact of IC and its components on financial performance of Chinese ecological protection and environmental governance companies during 2018–2021. In addition, the moderating effect of digital transformation between them is examined. IC is measured by the modified value added intellectual coefficient (MVAIC) model, and the measurement of digital transformation is based on text mining. The results suggest that IC can improve firm financial performance, especially during COVID-19. Physical capital, human capital (HC), and relational capital (RC) positively affect financial performance, while structural and innovation capitals have no significant impact. In addition, digital transformation strengthens the positive relationship between IC and its two elements (HC and RC) and financial performance. Heterogeneous analysis finds that the relationship between RC and innovation capital and financial performance is positive before COVID-19, and it is not significant during COVID-19. For highly leveraged companies, structural capital negatively affects financial performance, and RC has a positive impact. These impacts are not significant for low leveraged companies. This paper provides some new insights for managers who seek new ways to improve firm performance in the process of digital transformation.
Exogenous LEA proteins expression enhances cold tolerance in mammalian cells by reducing oxidative stress
Abstract Understanding the molecular mechanisms that confer cold resistance in mammalian cells might be relevant for advancing medical applications. This study aimed to exploit the protective function of Late Embryogenesis Abundant (LEA) proteins, known to provide resistance to low temperatures in extremophiles and plants, by their exogenous expression in mammalian cells, and compare their effects with the well characterized antioxidant, vitamin E. Remarkably, the expression of LEA proteins in mammalian cells exerted cold-protective effect similar to Vitamin E. LEA proteins preserved cell viability during cold stress and ensured a normal metabolic activity after warming. Their protective action was due to the mitigation of cold-induced mitochondrial stress and the overproduction of reactive oxygen species (ROS), leading in turn to enhanced cytoskeleton stability and decreased DNA damage. Our studies showed that plant-derived LEA proteins exhibit remarkable cold protection effects in mammalian cells through their potent antioxidant properties, which was found comparable to Vitamin E.
Estimation of stationary and non-stationary moving average processes in the correlation domain
This paper introduces a novel approach for the offline estimation of stationary moving average processes, further extending it to efficient online estimation of non-stationary processes. The novelty lies in a unique technique to solve the autocorrelation function matching problem leveraging that the autocorrelation function of a colored noise is equal to the autocorrelation function of the coefficients of the moving average process. This enables the derivation of a system of nonlinear equations to be solved for estimating the model parameters. Unlike conventional methods, this approach uses the Newton-Raphson and Levenberg–Marquardt algorithms to efficiently find the solution. A key finding is the demonstration of multiple symmetrical solutions and the provision of necessary conditions for solution feasibility. In the non-stationary case, the estimation complexity is notably reduced, resulting in a triangular system of linear equations solvable by backward substitution. For online parameter estimation of non-stationary processes, a new recursive formula is introduced to update the sample autocorrelation function, integrating exponential forgetting of older samples to enable parameter adaptation. Numerical experiments confirm the method’s effectiveness and evaluate its performance compared to existing techniques.
Who is American? A comprehensive analysis of the American = White/Foreign = Asian stereotype (2007–2023)
Perceived stress and coping strategies used by undergraduate dental students: An observational study
Studies around the world have reported that dental students experience higher stress compared to medical students. Prolonged and high perceived stress can be of a significant concern as it affects the personal, psychological, and professional well-being of the student, affecting quality of life. The aim of the study was to describe the perceived stress and coping strategies that undergraduate students at dental schools of Lahore, Pakistan employ. This observational study was conducted in year 2023 to report perceived stress and coping strategies among 720 undergraduate dental students of Lahore using modified Dental Environment Stress (DES) and brief Coping Orientation to Problems Experienced (COPE) questionnaires. Categorical variables such as sex, year of study (year 1 till 4), and responses to DES stress domains, stress-related items, COPE domains, and COPE-related items were computed into frequencies and percentages. Mean item scores of stress domains, stress-related items, COPE domains, and COPE-related items were presented with standard deviations (SD). Groups wise comparisons were done using Mann Whitney U and Kruskal Wallis H tests. P value < 0.05 was considered statistically significant. The majority of the undergraduate dental students perceived moderate amount of stress. Item “overload feeling due to huge syllabus” had the highest mean stress score (3.49±0.76) and “language barrier” had the lowest mean stress score (1.75±0.92). Female students had higher mean stress scores than the male students in all of the DES domains. Mean stress scores were higher in year 4 students for “workload”, “self-efficacy beliefs”, “faculty and administration”, “clinical training”, and “social stresses” compared to other years. “Religion” was the highest- and “denial” was the lowest-ranked coping strategies. Female students employed “active coping”, “positive reframing”, “religion”, “venting”, “self-blame”, “denial”, and “behavioral disengagement” coping strategies more than males. Moreover, final year dental students used “instrumental support”, “humor”, “self-blame”, “denial”, and “behavioral disengagement” coping strategies more than year 1 and 2 students. Sex and year of study can influence the degree of perceived stress and choice of coping strategies employed to overcome stressful situations. For the emotional, psychological, and professional well-being of undergraduate students, institutions must provide a nurturing and positive learning environment implementing strategies for stress prevention and management.
Construction of an evaluation indicator system for the integrated development of sports, culture and tourism based on tourist perceptions
A safe-enhanced fully closed-loop artificial pancreas controller based on deep reinforcement learning
Patients with type 1 diabetes and their physicians have long desired a fully closed-loop artificial pancreas (AP) system that can alleviate the burden of blood glucose regulation. Although deep reinforcement learning (DRL) methods theoretically enable adaptive insulin dosing control, they face numerous challenges, including safety and training efficiency, which have hindered their clinical application. This paper proposes a safe and efficient adaptive insulin delivery controller based on DRL. It employed ten tricks to enhance the proximal policy optimization (PPO) algorithm, improving training efficiency. Additionally, a dual safety mechanism of ’proactive guidance + reactive correction’ was introduced to reduce the risks of hyperglycemia and hypoglycemia and to prevent emergencies. Performance evaluations in the Simglucose simulator demonstrate that the proposed controller achieved an 87.45% time in range (TIR) median, superior to baseline methods, with a lower incidence of hypoglycemia, notably eliminating severe hypoglycemia and treatment failures. These encouraging results indicate that the DRL-based fully closed-loop AP controller has taken an essential step toward clinical implementation.
Study on spatial correlation and driving factors of industrial carbon emission in the Hefei metropolitan area based on SNA-QAP method
Implementing psychosocial interventions for teachers’ mental health: Protocol for integrating scoping review with teachers lived experiences in LMICs
Introduction Teachers are pivotal in shaping educational environments and student development but face significant occupational stress and high rates of mental problems. Despite the availability of various psychosocial interventions, comprehensive evidence of their effectiveness and implementation is limited for this occupational group, especially in low- and middle-income countries (LMICs). This mixed methods study aims to conduct a scoping review of characteristics, effectiveness, and implementation outcomes of psychosocial interventions for teachers’ mental health and mental problems, integrating these with teachers’ lived experiences to inform the implementation of mental health interventions in LMICs. Methods The study combines a scoping review with insights from an advisory group of teaching professionals with relevant lived experiences (PWLEs). The review will focus on examining psychosocial interventions studies promoting mental health or addressing mental problems among grade 1–12 school teachers of all genders, ages and contexts, except those working in specialized settings, such as special education centers, or disaster- or crisis-stricken zones. Intervention studies exclusively focusing on physical health or job-related outcomes will be excluded. Using pre-defined search terms, quantitative and qualitative research studies, including unpublished literature, will be searched across multiple databases. Titles and abstracts of identified studies will be screened against inclusion criteria, and the potentially relevant sources will be retrieved in full. Data will be extracted using a data extraction sheet developed for the study covering variables related to participant characteristics, intervention characteristics, study context, effectiveness and implementation outcomes. A purposively selected sample of 10 PWLEs will form the study advisory group and participate in four online workshop-group discussions. The meetings will include a presentation of the scoping review findings, followed by discussions on the relevance of these intervention packages for LMICs, adaptations needed to make them acceptable among school teachers and feasible for delivery in low-resourced settings like India. The synthesis of the data will employ narrative and thematic approaches to generate actionable insights for implementing psychosocial interventions in LMICs. Discussion This study will provide comprehensive evidence on the characteristics and outcomes of psychosocial interventions for teachers’ mental health and mental problems. By integrating insights from teachers with relevant lived experiences, the study will provide practical guidelines for adapting and implementing psychosocial interventions among school teachers in LMICs. Trial registration Review registration number: Open Science Framework, doi.org/10.17605/OSF.IO/GF59J.