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Abstract Glioma is the most common primary malignant tumor of the central nervous system in adults, characterized by high mortality, low cure rate and high recurrence rate. Among gliomas, glioblastoma multiforme (GBM) is the most malignant subtype. Currently, the standard treatment for patients with GBM is maximum surgical excision combined with radiotherapy and chemotherapy. But only a small percentage of patients benefit from this standard treatment. The tumor microenvironment plays an important role in the occurrence and development of most tumors. It is primarily composed of tumor cells, peripheral blood vessels, extracellular matrix, signaling molecules, stromal cells, and immune cells. The role of stromal cells in GBM has emerged as the focus of current research. The interaction among tumor, stromal, and immune cells within the tumor microenvironment can influence tumor development. Traditional research and drug therapy in glioma mainly focus on the tumor cells themselves, but recent studies have found that targeting stromal cells in the tumor microenvironment can also modulate tumor progression in GBM. Here, we review the influence of stromal cells in the tumor microenvironment of GBM on tumor cells and its related mechanism, as well as related molecular targets and signaling pathways, providing new ideas for the treatment and prognosis of GBM.

Abstract Background Increasing evidences suggest that nonalcoholic fatty liver disease (NAFLD) is associated with neuropsychiatric disorders. Nevertheless, whether there were causal associations between them remained vague. A causal association between neuropsychiatric disorders and NAFLD was investigated in this study. Methods We assessed the published genome-wide association study summary statistics for NAFLD, seven mental disorder-related diseases and six central nervous system dysfunction-related diseases. The causal relationships were first assessed using two-sample and multivariable Mendelian randomization (MR). Then, sensitivity analyses were performed, followed by a reverse MR analysis to determine whether reverse causality is possible. Finally, we performed replication analyses and combined the findings from the above studies. Results Our meta-analysis results showed NAFLD significantly increased the risk of anxiety disorders (OR = 1.016, 95% CI = 1.010–1.021, P value

Grinding is a critical method for enhancing the quality of worm tooth surfaces, and its process optimization has long been a significant research focus; however, existing methods are insufficient in addressing the nonlinearity and complexity inherent in the grinding of complex surfaces. In this study, a three-objective optimization function tailored for grinding complex spiral surfaces is developed and experimentally validated. We have successfully applied the innovative integration of the Multi-objective Grey Wolf Optimization Algorithm (MOGWO) and the optimization function to optimize the grinding process of the Roller Enveloping Worm Reducer (REWR). To account for actual working conditions, we developed constrained models for grinding ratio and machining rigidity and improved the boundary processing method for MOGWO optimization. The enhanced MOGWO demonstrates superior search capabilities during the optimization process, with its optimal solution outperforming traditional optimization algorithms. The optimized grinding process parameters reduce the grinding time by 17.41%, improve the grinding surface quality by 4.46%, and reduce the grinding cost by 1.12% compared with the conventional machining scheme. This provides practical guidance for optimizing the REWR and other complex surface grinding processes.

Neddylation, a type of protein post-translational modification that links the ubiquitin-like protein NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, the best-characterized substrates of neddylation are the Cullin protein family, which is the core subunit of the Cullin-RING E3 ubiquitin ligase complex and controls many important biological processes by promoting ubiquitination and subsequent degradation of various key regulatory proteins. The normal or abnormal process of protein neddylation in the central nervous system can lead to a series of occurrences of normal functions and the development of diseases, providing an attractive, reasonable, and effective targeted therapeutic strategy. Therefore, this study reviews the phenomenon of neddylation in the central nervous system and summarizes the corresponding substrates. Finally, we provide a detailed description of neddylation involved in CNS diseases and treatment methods that may be used to regulate neddylation for the treatment of related diseases.

Indole-3-acetic acid (IAA), as an important regulator of potato growth, seriously affects the growth and yield of potato. Although many studies have reported that IAA-producing Bacillus can promote plant growth, little research has been conducted on its synthesis pathway and molecular mechanisms. In this study, an IAA-producing strain WL35 was identified as Fitibacillus barbaricus, and its yield was 48.79 mg·L−1. The results of the pot experiments showed that WL35 significantly increased plant height, stem thickness, chlorophyll content, and number of leaves of potato plants by 31.68%, 30.03%, 32.93%, and 36.59%, respectively. In addition, in the field experiments, WL35-treated plants increased commercial potato yield by 16.45%, vitamin C content by 16.35%, protein content by 75%, starch content by 6.60%, and the nitrogen, phosphorus, and potassium accumulation by 9.98%, 12.70%, and 26.76%, respectively. Meanwhile, the synthetic pathway of WL35 was found to be dominated by the tryptophan-dependent pathway, the IAM, TAM, and IPA pathways worked together, and the pathways that played a role at different times were different. Furthermore, RNA-seq analysis showed that there were a total of 2875 DEGs regulated in the samples treated with WL35 seed dressing compared with the CK, of which 1458 genes were up-regulated and 1417 genes were down-regulated. Potato roots express differential genes enriched in processes such as carbohydrate metabolism processes and cellular polysaccharide metabolism, which regulate potato plant growth and development. The above results provide a theoretical basis for the further exploration of the synthesis pathway of IAA and its growth-promoting mechanism in potato.

IntroductionCerebro spinal fluid (CSF) leakage is common and might lead to severe postoperative complications after endoscopic transsphenoidal pituitary adenoma resection. However, the risk factors of postoperative CSF leakage are still controversial. This article presents a systematic review to explore the explicit risk factors of CSF leakage after endoscopic transsphenoidal pituitary adenomere section.MethodsPRISMA and AMSTAR guidelines were followed to assess the methodological quality of the systematic review. PubMed, Medline, Embase, Web of Science, Cochrane, Clinical Trails, CNKI, CBM, Wan Fang, and VIP databases were searched for all studies on postoperative CSF leak risk factors. The quality of the included studies was assessed by the Newcastle-Ottawa scale. Review Manager 5.4 software was used to calculate the pooled effect size of potential factors with statistical significance.ResultsA total of 6775 patients with pituitary adenoma across 18 articles were included, containing 482 cases of postoperative CSF leakage (accounting for 7.11%). All of the articles had a quality score > 5, indicating good quality. Meta-analysis showed that an increased risk of CSF leak was found for higher levels of BMI (MD=1.91, 95% CI (0.86,2.96), bigger tumor size [OR=4.93, 95% CI (1.41,17.26)], greater tumor invasion (OR=3.01, 95% CI (1.71, 5.31), the harder texture of tumor [OR=2.65, 95% CI (1.95,3.62)], intraoperative cerebrospinal fluid leakage [OR=5.61, 95% CI (3.53,8.90)], multiple operations [OR=2.27, 95% CI (1.60,3.23)].ConclusionBMI, multiple operations, tumor size, tumor invasion, hard texture, and intraoperative cerebrospinal fluid leakage are the risk factors of postoperative CSF leakage. Clinical doctors should pay attention to these risk factors, and conduct strict skull base reconstruction and careful postoperative management.

Potato common scab, caused mainly by Streptomyces scabies, causes surface necrosis and reduces the economic value of potato tubers, but effective chemical control is still lacking. In this study, an attempt was made to control potato common scab by inoculating potatoes with Bacillus velezensis (B. velezensis) and to further investigate the mechanism of biological control. The results showed that B. velezensis Y6 could reduce the disease severity of potato common scab from 49.92 ± 25.74% [inoculated with Streptomyces scabies (S. scabies) only] to 5.56 ± 1.89% (inoculated with S. scabies and Y6 on the same day) and increase the potato yield by 37.32% compared with the control under pot experiment in this study. Moreover, in the field trial, it was found that Y6 could also significantly reduce disease severity from 13.20 ± 1.00% to 4.00 ± 0.70% and increase the potato yield from 2.07 ± 0.10 ton/mu to 2.87 ± 0.28 ton/mu (p

The utilization of Erythritol/xylitol eutectic material for low-temperature thermal energy storage and thermal management holds great promise. However, its inability to undergo spontaneous nucleation and crystallization poses a significant obstacle. This research paper introduces a novel nucleation technique that combines gas injection agitation and seeding to address this issue. The study aims to investigate the impact of gas injection tube diameter, thermal environment, and gas injection duration on the nucleation and crystallization characteristics of the material. Experimental analysis reveals that, under optimal conditions, the solidification enthalpy reaches 203.1 J/g, equivalent to 85% of the melting enthalpy. Additionally, the material exhibits excellent thermal cycle stability, with no observed phase separation or deterioration after 100 heating and cooling cycles. Furthermore, the influence of Multi-Walled Carbon Nanotube (MWCNT) nanoparticle additives on nucleation is explored. Different MWCNT additive mass fractions are compared. The obtained results underscore the significance of understanding the effects of gas injection parameters and nanoparticle additives on nucleation and crystallization processes. The enhanced solidification enthalpy, remarkable thermal cycle stability, and insights into MWCNT effects pave the way for broader applications of this promising phase change material in thermal energy storage and thermal management.

Abstract In gear transmission, temperature rise has a non-negligible impact on the accuracy, noise and transmission efficiency. However, there is no relevant research on the temperature rise of the anti-backlash single-roller enveloping hourglass worm (ASEHW) gear. To solve this problem, based on tribology principle and Hertz contact theory, the thermal power calculation method of the ASEHW gear was proposed for the first time and thermal analysis was carried out by Ansys software. The bulk temperature of the ASEHW gear under four different rotating speed (300 r/min, 600 r/min, 900 r/min, 1200 r/min) is calculated. The main factors causing temperature rise of the ASEHW gear are analyzed theoretically. Meanwhile, an experimental study is performed to verify the simulation results and validate the theory methods. The theory presented in this paper provides a solution for the thermal power calculation of ASEHW gear. This research provides a theoretical basis for further optimization of ASEHW gear.

Background: Canadian specialist residency training programs are implementing a form of competency-based medical education (CBME) that requires the assessment of entrustable professional activities (EPAs). Dashboards could be used to track the completion of EPAs to support program evaluation. Methods: Using a design-based research process, we identified program evaluation needs related to CBME assessments and designed a dashboard containing elements (data, analytics, and visualizations) meeting these needs. We interviewed leaders from the emergency medicine program and postgraduate medical education office at the University of Saskatchewan. Two investigators thematically analyzed interview transcripts to identify program evaluation needs that were audited by two additional investigators. Identified needs were described using quotes, analytics, and visualizations. Results: Between July 1, 2019 and April 6, 2021 we conducted 17 interviews with six participants (two program leaders and four institutional leaders). Four needs emerged as themes: tracking changes in overall assessment metrics, comparing metrics to the assessment plan, evaluating rotation performance, and engagement with the assessment metrics. We addressed these needs by presenting analytics and visualizations within a dashboard. Conclusions: We identified program evaluation needs related to EPA assessments and designed dashboard elements to meet them. This work will inform the development of other CBME assessment dashboards designed to support program evaluation.

Background: Canadian specialist residency training programs are implementing a form of competency-based medical education (CBME) that requires frequent assessments of entrustable professional activities (EPAs). Faculty struggle to provide helpful feedback and assign appropriate entrustment scores. CBME faculty development initiatives rarely incorporate teaching metrics. Dashboards could be used to visualize faculty assessment data to support faculty development. Methods: Using a design-based research process, we identified faculty development needs related to CBME assessments and designed a dashboard containing elements (data, analytics, and visualizations) meeting these needs. Data was collected within the emergency medicine residency program at the University of Saskatchewan through interviews with program leaders, faculty development experts, and faculty participating in development sessions. Two investigators thematically analyzed interview transcripts to identify faculty needs that were audited by a third investigator. The needs were described using representative quotes and the dashboard elements designed to address them. Results: Between July 1, 2019 and December 11, 2020 we conducted 15 interviews with nine participants (two program leaders, three faculty development experts, and four faculty members). Three needs emerged as themes from the analysis: analysis of assessments, contextualization of assessments, and accessible reporting. We addressed these needs by designing an accessible dashboard to present contextualized quantitative and narrative assessment data for each faculty member. Conclusions: We identified faculty development needs related to EPA assessments and designed dashboard elements to meet them. The resulting dashboard was used for faculty development sessions. This work will inform the development of CBME assessment dashboards for faculty.

This paper presents a study to investigate the effects of the shape of rollers in high precision enveloping speed reducer on the reducer’s lubrication performance. Theoretical models for the precision speed reducer with cylindrical and conical rollers as its transmission components were constructed at first based on the meshing theory. Next, numerical analysis was conducted investigate the lubrication status of the speed reducers with different types of rollers at four rotation speeds using ParticleWorks. The moving particle semi-implicit method embedded in that software was used to model the reducers and the inside lubricant flow. A sequence of tests was performed to inspect the transmission efficiency of the reducers at four different rotation speeds. Experimental data were compared to the simulation predictions. Comparisons showed that the data measured from the experiments matched the simulation results very well. Both experimental and computational results confirmed that the lubrication performance of the enveloping speed reducer with conical rollers is better than that of the speed reducer with cylindrical rollers. It has also been proven that the method of using the churning power losses to assess the effects of the shape of the rollers on the roller enveloping speed reducer’s lubrication behavior is highly reliable.

With the era of big data approaching, the number of software systems, their dependencies, as well as the complexity of the individual system is becoming larger and more intricate. Understanding these evolving software systems is thus a primary challenge for cost-effective software management and maintenance. In this paper we perform a case study with evolving code clones. The programmers often need to manually analyze the co-evolution of clone fragments to decide about refactoring, tracking, and bug removal. However, manual analysis is time consuming, and nearly infeasible for a large number of clones, e.g., with millions of similarity pairs, where clones are evolving over hundreds of software revisions.We propose an interactive visual analytics system, Clone-World, which leverages big data visualization approach to manage code clones in large software systems. Clone-World, gives an intuitive yet powerful solution to the clone analytic problems. Clone-World combines multiple information-linked zoomable views, where users can explore and analyze clones through interactive exploration in real time. User studies and experts’ reviews suggest that Clone-World may assist developers in many real-life software development and maintenance scenarios. We believe that Clone-World will ease the management and maintenance of clones, and inspire future innovation to adapt visual analytics to manage big software systems. Keywords: Visual analytics, Software clones, Multivariate networks

To access the enhancement effect of the topology optimization and porous foam structure, numerical studies were conducted to investigate the heat conduction enhancement (by metal foam, graphite foam, topologically optimized fins, and combinations of metal foam and topologically optimized fins) of phase change material (PCM (n-octadecane)) based tubular thermal energy storage unit for spacecraft. The results showed that metal foam performed better than topologically optimized fins and a combination of metal foam and topology optimized fins, of which conductive material, unit mass, and volume fraction of PCM were the same. Graphite foam (140 W/(m·K)) had the best heat transfer enhancing effect, making PCM melt much faster than other enhancing methods investigated. A multi-criteria decision-making (MCDM) method integrated with the combined weight and TOPSIS method was introduced to evaluate the preferred alternatives’ performance based on the energy storage time, equivalent density, and energy storage. The evaluation pointed out that 3% topologically optimized aluminum fins with 98% copper foam had the best comprehensive performance. This study guided the optimal design of latent heat thermal energy storage units for spacecraft under microgravity.

A process of modeling and reconstructing human head injuries involved in traffic crashes based on ABAQUS/Explicit is presented in this paper. A high-fidelity finite element (FE) model previously developed by the authors is employed to simulate a real accident case that led to head injury. The most probable head impact position informed by CT images is used for the FE modeling and simulation since the head impact position is critical for accident reconstruction and future analysis of accidents that involve human head injuries. Critical von Mises stress on the skull surface of the head model is chosen as the evaluation criterion for the head injury and FE simulations on 60 cases with various human head—concrete ground impact conditions (impact speeds and angles) were run to obtain those stress values. The FE simulation results are compared with the CT images to determine the minimum speed that will cause skull fracture and the corresponding contact angle at that speed. Our study shows that the minimum speed that would cause skull fracture is 3.5 m/s when the contact angle between the occipital position of the injured head and the ground is about 30°. Effects of the impact speed and the contact angle on the maximum von Mises stress of the head model are revealed from the simulations. The method presented in this paper will help forensic pathologists to examine the head impact injuries and find out the real reasons that lead to those injuries.

In this study, the moving particle semi-implicit (MPS) method is employed for numerical simulation of flow field in gearbox of high-speed railway trains so as to understand the lubrication mechanism and mode in the gearbox during high-speed operation. A high-fidelity 3D model for a high-speed train gearbox under actual working conditions is created for the first time. RecurDyn and ParticleWorks co-simulation is conducted to acquire the flow field distribution in the gearbox under the coupling of multi-fields and to calculate the churning losses. Effects of key parameters including rotation speed, viscosity, and immersion depth on the churning power losses of the gearbox are investigated to determine their influences on the lubrication performance of the gearbox. Those results form a theoretical base for futuristic optimization of the high-speed train gearboxes.

The new precision transmission system-Anti-backlash roller enveloping hourglass worm gears are now widely employed in many industrial sectors such as robot joint design, packaging production line, and CNC (computer numerical control) machine tools. Therefore, it is of great interest to have knowledge of their corresponding transmission principles that are seldom discussed in the literature. Using the theories of differential geometry and gear meshing, the objective of this paper is to analyze and compare meshing characteristics of anti-backlash single- and double-roller enveloping hourglass worm gears in terms of their transmission principle, engagement equation, induced normal curvature, lubrication angle, autorotation angle, entrainment velocity, helix angle, and distribution of contact curves. The major differences between these two roller enveloping hourglass worms are theoretically investigated in this work. Our results show that the anti-backlash single-roller enveloping hourglass worm (ASEHW) gears provide better performance with respect to gear meshing and transmission than the anti-backlash double-roller enveloping hourglass worm (ADEHW) gears. In addition, compared with the ADEHW gears, the ASEHW gears are easier to fabricate, install, and calibrate. However, the ADEHW gears are more auto-adjustable in eliminating gear backlash. Our study puts forward a theoretical background for futuristic design, application, and promotion of the anti-backlash roller enveloping hourglass worm gears.

Diabetes is a global epidemic, and its pathogenesis involves multiple factors. Diabetic peripheral neuropathy (DPN) is one of its clinical complications, which brings a serious burden to the lives of patients. Pandanus tectorius fruits (PTF) extract has attracted much attention due to its rich bioactive components and is considered to have potential effects in treating DPN. The present study aims to deeply explore the molecular mechanism of PTF extract in treating diabetic peripheral neuropathy, focusing on the regulatory effect of the Nrf2/Keap1 signalling pathway. The blood glucose changes and behavioural changes of DPN rats before and after PTF treatment were detected. Histological myelin staining was performed using Luxol fast blue (LFB) staining. TUNEL staining was used to observe the apoptosis of sciatic nerve cells. TEM observation of the ultrastructure of dorsal root ganglion. ELISA and kits detect NGF, IGF-1, VEGF, SOD, GSH-Px, and malondialdehyde (MDA). Western blot detects Nrf2, Keap1, HO-1 and NQO1. This experiment found that PTF extract has significant blood glucose control and analgesic effects on DPN rats. PTF extract can also inhibit the apoptosis of sciatic nerve cells in DPN rats and protect the structural integrity of myelin sheaths. The ultrastructure of dorsal root ganglia was improved after PTF treatment. The neuroactive factors (IGF-1, VEGF) in rats with DPN under a high-fat diet were significantly reduced, NGF was overexpression, the oxidative stress-related factors SOD and GSH-Px were reduced, and the levels of MDA were increased. After treatment with PTF, the positive drug a-lipoic acid reversed these abnormalities, enhanced levels of neuroactive factors, and mitigated oxidative stress. Western blot analysis showed that in DPN, the expression of Nrf2, HO-1 and NQO1 proteins in the sciatic nerve was down-regulated, Keap1 was overexpression, while PTF and a-lipoic acid treatment led to their upregulation. Adding the Nrf2 inhibitor Brusatol to the DPN + PTF group inhibited the up-regulating effect of PTF on these proteins. In summary, PTF extract can effectively reduce blood glucose and pain perception in DPN rats, promote antioxidant capacity, and protect the sciatic nerve through the Nrf2/Keap1 signalling pathway, thereby achieving the purpose of treating DPN. [ABSTRACT FROM AUTHOR]