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Abstract De novo purine synthesis metabolism plays a crucial role in tumor cell survival and malignant progression. However, the specific impact of this metabolic pathway on chemoresistance in ovarian cancer remains unclear. This study aims to elucidate the influence of de novo purine synthesis on chemoresistance in ovarian cancer and its underlying regulatory mechanisms. We analyzed metabolic differences between chemosensitive and chemoresistant ovarian cancer tissues using mass spectrometry-based metabolomics. Cell growth, metabolism, chemoresistance, and DNA damage repair characteristics were assessed in vitro using cell line models. Tumor growth and chemoresistance were assessed in vivo using ovarian cancer xenograft tumors. Intervention of purines and NEK6-mediated purine metabolism on chemoresistance was investigated at multiple levels. Chemoresistant ovarian cancers exhibited higher purine abundance and NEK6 expression. Inhibiting NEK6 led to decreased de novo purine synthesis, resulting in diminished chemoresistance in ovarian cancer cells. Mechanistically, NEK6 directly interacted with FOXO3, contributing to the phosphorylation of FOXO3 at S7 through its kinase activity, thereby inhibiting its nuclear translocation. Nuclear FOXO3 promoted FBXW7 transcription, leading to c-MYC ubiquitination and suppression of de novo purine synthesis. Paeonol, by inhibiting NEK6, suppressed de novo purine synthesis and enhanced chemosensitivity. The NEK6-mediated reprogramming of de novo purine synthesis emerges as a critical pathway influencing chemoresistance in ovarian cancer. Paeonol exhibits the potential to interfere with NEK6, thereby inhibiting chemoresistance.

The development and creation of innovative therapeutic supplements and medications with extraordinary efficacy for addressing severe diabetes are of utmost importance to both developing and developed nations. A bio-inspired method has been documented for producing copper nanoparticles (CuNPs) using Pistacia atlantica leaf extract as a natural stabilizing agent. This approach is applicable, easy, and environmentally friendly, as it avoids using any toxic or harmful reagents. The CuNPs that were synthesized through biological processes underwent characterization using sophisticated physicochemical methods such as energy-dispersive X-ray spectroscopy, transmission electron microscopy, field emission-scanning electron microscopy, and Fourier-transformed infrared spectroscopy. It is confirmed that CuNPs exhibit a spherical structure, with an average size ranging from approximately 30 to 70 nm. Diabetes was induced in vivo through a fructose-enriched diet combined with streptozotocin. Half the subjects were administered CuNPs (100 µg/kg) via oral gavage. In contrast to the animals that were given regular food, the diabetic animals revealed an increase in serum fasting glucose level and a decrease in glucose tolerance. The administration of CuNPs had a significant impact on reducing glucose intolerance and fasting hyperglycemia. Additionally, it helped alleviate the negative effects of diabetes on cardiac output and work. Furthermore, utilizing CuNPs effectively hindered the rise in cardiac signal transducer and activator of transcription 3-phosphorylation caused by diabetes. The findings from this investigation provide evidence of the therapeutic benefits of CuNPs in mitigating diabetes-induced cardiac dysfunction in rats.

Abstract Flueggea virosa (Roxb. ex Willd.) Royle, an evergreen shrub and small tree in the Phyllanthaceae family, holds significant potential in garden landscaping and pharmacological applications. However, the lack of genomic data has hindered further scientific understanding of its horticultural and medicinal values. In this study, we have assembled a haplotype-resolved genome of F. virosa for the first time. The two haploid genomes, named haplotype A genome and haplotype B genome, are 487.33 Mb and 477.53 Mb in size, respectively, with contig N50 lengths of 31.45 Mb and 32.81 Mb. More than 99% of the assembled sequences were anchored to 13 pairs of pseudo-chromosomes. Furthermore, 21,587 and 21,533 protein-coding genes were predicted in haplotype A and haplotype B genomes, respectively. The availability of this chromosome-level genome fills the gap in genomic data for F. virosa and provides valuable resources for molecular studies of this species, supporting future research on speciation, functional genomics, and comparative genomics within the Phyllanthaceae family.

Abstract The impact of the Coronavirus Disease 2019 (COVID-19) on society is continuous, resulting in negative psychological consequences. Given the vulnerability and sensitivity to the environment among preschool children, their emotional and behavioral problems deserve more attention. The current study aimed to explore the impact of the epidemic on preschool children’s mental health by determining the pooled prevalence of emotional and behavioral problems amidst the Coronavirus Disease 2019 pandemic and to reveal potential reasons for variations between studies. Published studies were searched in Embase, PubMed, ProQuest, PsycINFO, Web of Science, CNKI, and Wanfang. Based on the inclusion criteria outlined in this study, a total of 10 studies encompassing 38,059 participants were incorporated. Employing a random-effect model for estimating the prevalence of emotional and behavioral problems, the results revealed a pooled prevalence rate of 24.3% (95% CI, 0.15–0.38; I²=99.9%) among preschool children. This rate surpasses the pre-outbreak prevalence observed in different countries, signifying a detrimental influence of the epidemic on the mental well-being of preschoolers. Therefore, mental health care and recovery are essential for the vulnerable group during and after the public health crisis. Specific emotional and behavioral problems among preschool children are expected to be researched in the future to provide more targeted guidance for intervention.

Abstract Endowing the widely-used synthetic polymer nylon with high-performance organic room-temperature phosphorescence would produce advanced materials with a great potential for applications in daily life and industry. One key to achieving this goal is to find a suitable organic luminophore that can access the triplet excited state with the aid of the nylon matrix by controlling the matrix-luminophore interaction. Herein we report highly-efficient room-temperature phosphorescence nylons by doping cyano-substituted benzimidazole derivatives into the nylon 6 matrix. These homogeneously doped materials show ultralong phosphorescence lifetimes of up to 1.5 s and high phosphorescence quantum efficiency of up to 48.3% at the same time. The synergistic effect of the homogeneous dopant distribution via hydrogen bonding interaction, the rigid environment of the matrix polymer, and the potential energy transfer between doped luminophores and nylon is important for achieving the high-performance room-temperature phosphorescence, as supported by combined experimental and theoretical results with control compounds and various polymeric matrices. One-dimensional optical fibers are prepared from these doped room-temperature phosphorescence nylons that can transport both blue fluorescent and green afterglow photonic signals across the millimeter distance without significant optical attenuation. The potential applications of these phosphorescent materials in dual information encryption and rewritable recording are illustrated.

The interrelationship of science and engineering and the recent inclusion of engineering in K-12 science standards have promoted the incorporation of engineering design in science classrooms. However, empirical studies on the impacts of engineering design on science learning show mixed findings and indicate that factors such as the complexity of design tasks, a lack of connections between design tasks and the underlying science concepts, and the limited experience with engineering among science teachers can influence learning gains from design activities. One useful approach for addressing these challenges is through the use of technologies such as interactive simulations, which have become increasingly prevalent in STEM education. In the present study, we used a simulation to investigate the effects of task context (science vs. engineering) on students' investigation behaviors and their understanding of science concepts. Furthermore, considering the relative novelty and complexity of an engineering context to many students, we examined how structuring students' responses in the engineering context affects their behaviors and learning. A total of 349 high school students were randomly assigned to one of three conditions: science, structured engineering, and unstructured engineering. In the science condition, students used the simulation to investigate the effects of four variables on the saturation concentration of solutions. Using the same simulation, students in the structured and unstructured engineering conditions were directed to recommend the optimal variable values that meet a set of given constraints and maximize the saturation concentration for a commercial product. The only difference between the two engineering conditions was whether structuring was provided in the response fields presented to students as they entered responses for the target variables. Results suggested that the engineering context stimulated students to engage in more comprehensive investigation behaviors as compared to the science context. In contrast, students in the science condition exhibited more systematic behaviors. However, the increased comprehensiveness of behaviors in the engineering conditions did not translate into significantly greater learning of the science content in these conditions, indicating that students might have focused on the surface features associated with the engineering goal without making deep connections between the two domains. Furthermore, structuring students' responses within an engineering context as used in the current study did not lead to significant differences in investigation behaviors or learning outcomes.

Abstract Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT‐proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31–80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non‐LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the “Clinical characteristics” model, the “Biomarkers” model (each based on their respective variables), and the “Clinical characteristics + Biomarkers” model, which amalgamated both sets of variables. The results revealed that the “Clinical characteristics + Biomarkers” model surpassed the baseline models in performance (AUC values of the “Clinical characteristics + Biomarkers” model, the “Biomarkers” model, and the “Clinical characteristics” model were .83, .75, and .74, respectively; P

This exploratory study investigated the behaviors and content of onscreen calculator usage by a nationally representative sample of eighth-grade students who responded to items from the 2017 National Assessment of Educational Progress mathematics assessment. Meaningful features were generated from the process data to infer whether students spontaneously used calculators for mathematical problem solving, how frequently and when they used them, and the nature of the operations performed on calculators. Sequential pattern mining was applied on sequences of calculator keystrokes to obtain patterns of operations that were representative of students' problem-solving strategies or processes. Results indicated that higher scoring students not only were more likely to use calculators, but also used them in a more goal-driven manner than lower scoring students.

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

Objective To assess the effects of telerehabilitation on clinical symptoms, physical function, psychological function and quality of life (QoL) in patients with post-COVID-19.Design Systematic review and meta-analysis of randomised controlled trials (RCTs).Data sources PubMed, Web of Science, Embase and Cochrane Library were searched for publications from 1 January 2020 to 17 April 2024.Eligibility criteria RCTs investigating the effects of telerehabilitation in patients with post-COVID-19 were included. The outcomes of interest encompassed clinical symptoms, physical function, psychological function and QoL. Only studies reported in English were included.Data extraction and synthesis Two reviewers independently extracted data and evaluated the risk of bias. Statistical analysis was conducted using Review Manager V.5.3, employing mean difference (MD) with a 95% CI, and the corresponding P value was used to ascertain the treatment effect between groups. Heterogeneity was quantified using the I2 statistic. The quality of evidence was assessed by GRADE.Results 16 RCTs (n=1129) were included in this systematic review, 15 of which (n=1095, 16 comparisons) were included in the meta-analysis. The primary pooled analysis demonstrated that, compared with no rehabilitation or usual care, telerehabilitation can improve physical function (measured by 30 s sit-to-stand test [6 RCTs, n=310, MD=1.58 stands, 95% CI 0.50 to 2.66; p=0.004]; 6 min walking distance [6 RCTs, n=324, MD=76.90 m, 95% CI 49.47 to 104.33; p

Abstract Stimulated by the recent researches of black hole thermodynamics for black hole with Newman–Unti–Tamburino (NUT) parameter, we investigate the thermodynamics and weak cosmic censorship conjecture for a Kerr–Newman Taub–NUT black hole. By defining the electric charge as a Komar integral over the event horizon, we construct a consistent first law of black hole thermodynamics for a Kerr–Newman Taub–NUT black hole through Euclidean action. Having the first law of black hole thermodynamics, we investigate the weak cosmic censorship conjecture for the black hole with a charged test particle and a complex scalar field. We find that an extremal black hole cannot be destroyed by a charged test particle and a complex scalar field. For a near-extremal black hole with small NUT parameter, it can be destroyed by a charged test particle but cannot be destroyed by a complex scalar field.