Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction.

BACKGROUND: Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. METHODS: Clinical samples from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021, cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. RESULTS: NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. CONCLUSIONS: Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Effect of Ultraviolet Radiation on Properties of Ge2Sb2Te5 Phase Change Films.

With the expanding utilization of space technology, the stability of electronic components' performance in radiation environments has garnered significant attention. In this study, we prepared Ge2Sb2Te5 phase change films and memory units on silicon substrates to explore the influence of ultraviolet (UV) radiation on their characteristics. The experimental findings revealed that UV irradiation at a power density of 450 mW/cm2 decreased the amorphous resistance and thermal stability of Ge2Sb2Te5 films, impeding their multistage storage performance. Nevertheless, the amorphous state could still undergo effective transformation into a crystalline state. Furthermore, UV irradiation triggered the photoelectric effect, narrowing the band gap and causing a redshift of the Raman peak in amorphous films. Remarkably, the surface properties of Ge2Sb2Te5 films remained unchanged under irradiation. The phase change memory device based on Ge2Sb2Te5 film retained its SET-RESET conversion capability at a pulse width of 100 ns post-UV irradiation, demonstrating resilience against UV radiation. This study offers the practical insights for the application of phase change memory in space radiation environments.

Research on the correlation between clinical nurses' self-efficacy, future time perspective, and occupational burnout.

Background: The number of clinical nurses in China experiencing professional burnout is increasing yearly, posing a serious challenge to the public health sector. Implementing effective intervention strategies is key to reducing the level of occupational burnout. At present, training aimed at alleviating occupational burnout among clinical nurses is very limited, with common training programs focusing on addressing external factors of occupational burnout rather than the internal cognitive issues of clinical nurses. Self-efficacy and future time perspective are both aspects of an individual's internal self-cognition. Meanwhile, the relationship between clinical nurses' self-efficacy, future time perspective, and occupational burnout is not clear, and further research is needed to verify this. Objective: This study aims to reveal the relationship between clinical nurses' self-efficacy, future time perspective, and occupational burnout, and to explore the mediating role of future time perspective between self-efficacy and occupational burnout among clinical nurses, providing a scientific reference for training directions to improve occupational burnout. Methods: This study used a cross-sectional design, conducting a questionnaire survey with 529 practicing clinical nurses using the General Demographics Questionnaire (GDQ), the General Self-Efficacy Scale (GSES), the Zimbardo Time Perspective Inventory (ZTPI), and the Maslach Burnout Inventory-General Survey (MBI-GS). SPSS software version 26.0 was used to analyze the correlation between variables, and AMOS 26.0 was used to test the mediation effect. Results: Clinical nurses' self-efficacy had a negative predictive effect on occupational burnout (r = -0.503, p < 0.001). Future time perspective showed significant differences in regression coefficients on both the paths of self-efficacy (r = 0.615, p < 0.001) and occupational burnout (r = -0.374, p < 0.001). Future time perspective played a partial mediating role between self-efficacy and occupational burnout, accounting for 33.8% of the total effect. Conclusion: This study suggests a significant correlation between clinical nurses' self-efficacy, future time perspective, and occupational burnout. Self-efficacy can directly affect occupational burnout in clinical nurses and can also indirectly affect occupational burnout through the future time perspective.

Burden of multiple high-risk factors in pregnancy before and after the universal two-child policy in Chinese women: An observational study.

Background: The prevalence of high-risk pregnancy increased after the implementation of two-child policy in China, but the impact of this policy change on the burden and profile of multiple high-risk factors in pregnancy (MHFP) has been insufficiently explored. We hypothesised that the profile of MHFP might have changed after the two-child policy was implemented and aimed to estimate the prevalence, intercorrelation, and outcomes of MHFP before and after its introduction. Methods: We obtained data on the population of pregnant women before (2015) and after (2020/2021) the implementation of universal two-child policy in Huai'an. We then included 33 risk factors in our analysis based on the Five-Colour Management framework and defined MHFP as an individual having two or more of these factors. We also estimated the changes of the prevalence of each single factor and their coexistence. Lastly, we performed a network analysis to assess the intercorrelations across these factors and used logistic regression models to evaluate MHFP-related pregnancy outcomes. Results: We observed an increase in the prevalence of MHFP after the implementation of the universal two-child policy (25.8% in 2015 vs 38.4% in 2020/2021, P < 0.01). Chronic conditions (e.g. gestational diabetes mellitus, abnormal body mass index) had the largest increase among the included factors, while cardiovascular disease and hypertensive disorders were central factors of the network structures. The correlations of advanced maternal age with abnormal pregnancy histories and scarred uteri increased significantly from 2015 to 2020/2021. MHFP was associated with multiple pregnancy outcomes, including preterm birth (adjusted odds ratio (aOR) = 2.57; 95% confidence interval (CI) = 2.39-2.75), low birthweight (aOR = 2.77; 95% CI = 2.54-3.02), low Apgar score (aOR = 1.41; 95% CI = 1.19-1.67), perinatal death (aOR = 1.75; 95% CI = 1.44-2.12), and neonatal death (aOR = 1.76; 95% CI = 1.42-2.18). Moreover, an increasing number and certain combinations of MHFP were associated with higher odds of pregnancy outcomes. For example, the aOR of preterm birth increased from 1.67 (95% CI = 1.52-1.87) for one risk factor to 8.03 (95% CI = 6.99-9.22) for ≥4 risk factors. Conclusions: Chinese women experienced a higher burden of multiple high-risk factors after the introduction of the two-child policy, particularly those with advanced maternal age, obesity, and chronic conditions. Strategies targeting chronic conditions for women with MHFP should be prioritised and a shift to a multiple-factor-oriented framework is needed in the expanding Chinese maternal health care system.

The Role of Interferon Regulatory Factors in Liver Diseases.

The interferon regulatory factors (IRFs) family comprises 11 members that are involved in various biological processes such as antiviral defense, cell proliferation regulation, differentiation, and apoptosis. Recent studies have highlighted the roles of IRF1-9 in a range of liver diseases, including hepatic ischemia-reperfusion injury (IRI), alcohol-induced liver injury, Con A-induced liver injury, nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). IRF1 is involved in the progression of hepatic IRI through signaling pathways such as PIAS1/NFATc1/HDAC1/IRF1/p38 MAPK and IRF1/JNK. The regulation of downstream IL-12, IL-15, p21, p38, HMGB1, JNK, Beclin1, ß-catenin, caspase 3, caspase 8, IFN-γ, IFN-ß and other genes are involved in the progression of hepatic IRI, and in the development of HCC through the regulation of PD-L1, IL-6, IL-8, CXCL1, CXCL10, and CXCR3. In addition, IRF3-PPP2R1B and IRF4-FSTL1-DIP2A/CD14 pathways are involved in the development of NAFLD. Other members of the IRF family also play moderately important functions in different liver diseases. Therefore, given the significance of IRFs in liver diseases and the lack of a comprehensive compilation of their molecular mechanisms in different liver diseases, this review is dedicated to exploring the molecular mechanisms of IRFs in various liver diseases.

How does family functioning contribute to academic-related outcomes of Chinese adolescents: the mediating role of spirituality.

While family functioning is crucial to adolescent developmental outcomes, the mediating role of spirituality in the relationship between family functioning and academic-related outcomes of adolescents has been sparsely explored, particularly in non-Western contexts. To address this gap, based on a short-term longitudinal study, we examined the influence of family functioning on the academic values and academic anxiety of 4,981 Chinese adolescents in Sichuan, China, with spirituality as the mediator. We gathered data from students aged 11 and above at Wave 1 and at six months later (Wave 2). Analysis utilizing structural equation modeling indicated that prior family functioning positively and negatively predicted subsequent academic values and academic anxiety respectively, with spirituality as a significant mediator. Theoretically, this study helps to build up a conceptual model on how family functioning and spirituality of adolescents shape academic values and academic anxiety of adolescents. Practically, the present findings highlight the significance of enhancing family functioning and adolescent spirituality to help adolescents strive for academic success.

Research on Improved Crystallization Properties and Underlying Mechanism of the Sb2Te3 Phase-Change Thin Film by Inserting Sn15Sb85 Layers.

As a non-volatile semiconductor memory technology, phase-change memory has a wide range of application prospects as a result of the excellent comprehensive performance. In this paper, multilayer thin films based on Sb2Te3 material were designed and prepared by inserting the Sn15Sb85 layer. The thermal and electrical properties of superlattice-like Sb2Te3/Sn15Sb85 phase-change films can be adjusted by controlling the thickness ratio of Sb2Te3/Sn15Sb85. In comparison to the monolayer Sb2Te3 film, the multilayer layer Sb2Te3/Sn15Sb85 materials have a higher crystallization temperature, larger crystallization activation energy, and longer data lifetime, indicating the great improvement of thermal stability. The changes in the phase structure and vibrational modes of multilayer Sb2Te3/Sn15Sb85 films were characterized by X-ray diffraction and Raman spectroscopy, respectively. The presence of Sn15Sb85 layers restrains grain growth and refines the grain size. The multilayer Sb2Te3/Sn15Sb85 films exhibit better surface flatness, smaller surface potential undulation, and lower thickness variations than single-layer Sb2Te3. Phase-change memory cells based on the [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 thin film has a lower threshold voltage (1.9 V) and threshold current (3.1 µA) compared to the Ge2Sb2Te5 film. Meanwhile, the electrical heating model of a phase-change memory cell based on a [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 multilayer structure was established by multiphysics coupling analysis, proving the great improvement in heat transfer performance and efficiency. The experimental and theoretical studies confirm that the insertion of the Sn15Sb85 layer can significantly improve the crystallization properties of Sb2Te3 films, paving the way for optimizing the phase-change materials by regulating the microstructural parameters.

Validation of a Chinese Positive Youth Development Scale: Dimensionality and factorial invariance.

For a multi-dimensional measure of positive youth development (PYD), its factor structure should be invariant across groups and over time. This study examined the factorial validity of the 44-item short form of the "Chinese Positive Youth Development Scale" (CPYDS-SF) that assesses 15 dimensions of PYD attributes. Using two waves of longitudinal data with a one-year interval in between, this study examined the factor structure of the scale and whether the structure is invariant between gender groups and across time. The data were collected from 3,328 adolescents at Wave 1 and 3,638 adolescents at Wave 2, with a matched sample of 2,905 adolescents (mean age = 12.57 ± 0.72 at Wave 1; 49.54% girls). Confirmatory factor analysis revealed that the 15-factor structure fitted the data well. The findings of invariance tests further supported this structure's invariance across gender and time, indicating a stable factor structure of CPYDS-SF among Chinese adolescents. These findings suggest that CPYDS-SF can be used to examine gender differences and the longitudinal development of PYD qualities among Chinese adolescents.

White adipose tissue in metabolic associated fatty liver disease.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a prevalent chronic liver condition globally, currently lacking universally recognized therapeutic drugs, thereby increasing the risk of cirrhosis and hepatocellular carcinoma. Research has reported an association between white adipose tissue and MAFLD. SCOPE OF REVIEW: White adipose tissue (WAT) is involved in lipid metabolism and can contribute to the progression of MAFLD by mediating insulin resistance, inflammation, exosomes, autophagy, and other processes. This review aims to elucidate the mechanisms through which WAT plays a role in the development of MAFLD. MAJOR CONCLUSIONS: WAT participates in the occurrence and progression of MAFLD by mediating insulin resistance, inflammation, autophagy, and exosome secretion. Fibrosis and restricted expansion of adipose tissue can lead to the release of more free fatty acids (FFA), exacerbating the progression of MAFLD. WAT-secreted TNF-α and IL-1ß, through the promotion of JNK/JKK/p38MAPK expression, interfere with insulin receptor serine and tyrosine phosphorylation, worsening insulin resistance. Adiponectin, by inhibiting the TLR-4-NF-κB pathway and suppressing M2 to M1 transformation, further inhibits the secretion of IL-6, IL-1ß, and TNF-α, improving insulin resistance in MAFLD patients. Various gene expressions within WAT, such as MBPAT7, Nrf2, and Ube4A, can ameliorate insulin resistance in MAFLD patients. Autophagy-related gene Atg7 promotes the expression of fibrosis-related genes, worsening MAFLD. Non-pharmacological treatments, including diabetes-related medications and exercise, can improve MAFLD.

Pressure-Induced Topological Phase Transition and Large Rashba Effect in Halide Double Perovskite.

In general, hydrostatic pressure can suppress ferroelectric polarization and further reduce Rashba spin-splitting, considering the spin-orbit coupling effect. Here, we present the design of ferroelectric double perovskite Cs2SnSiI6, which exhibits the anomalous enhancement of Rashba spin-splitting parameters by pressure-induced ferroelectric topological order. The Rashba effect is nonlinear with the decrease in polarization under pressure and reaches a maximum at the pressure-induced Weyl semimetal (WSM) state between the transition from a normal insulator (NI) to a topological insulator (TI). Furthermore, we discover that controlling ferroelectric polarization with an electric field can also induce the topological transition with a large Rashba spin-splitting but under a lower critical pressure. These discoveries show a tunable gaint Rashba effect and pressure-induced topological phase transition for Cs2SnSiI6, which can promote future research on the interaction between the Rashba effect and topological order, and its application to new electronic and spintronic devices.

A novel hydrogen sulfide donor reduces neuroinflammation and seizures by activating ATP-sensitive potassium channels.

Epilepsy is a common neurological disorder worldwide. Hydrogen sulfide (H2S) has been found to have anti-seizure effects. However, its mechanism remains to be explored. In the present study, we showed that a novel H2S donor attenuated neuroinflammation by up-regulating ATP-sensitive potassium channel (KATP) expression to reduce seizures. The novel H2S donor significantly reduced the expression of TNF-α and increased the expression of IL-10 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. The modulatory effects of the H2S donor on inflammatory cytokines were prevented by glibenclamide, a common KATP channels blocker. The H2S donor promoted the expression of KATP channel subunits SUR2 and Kir6.1 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. In addition, the H2S donor reduced the electroencephalography amplitude of hippocampal epileptic waves and reduced seizures in pilocarpine-induced epileptic mice, which were also attenuated by glibenclamide. These results indicated that the novel H2S donor reduced seizures and regulated microglial inflammatory cytokines by activating KATP channels, which may provide a prospective therapeutic strategy for the anti-seizure effects of H2S donor.

Naringenin alleviates cognitive dysfunction in rats with cerebral ischemia/reperfusion injury through up-regulating hippocampal BDNF-TrkB signaling: involving suppression in neuroinflammation and oxidative stress.

Cognitive dysfunction is one of the common complications of cerebral ischemia-reperfusion (CI/R) injury after ischemic stroke. Neuroinflammation and oxidative stress are the core pathological mechanism of CI/R injury. The activation of brain derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling antagonize cognitive dysfunction in a series of neuropathy. Naringenin (NAR) improves cognitive function in many diseases, but the role of NAR in CI/R injury-induced cognitive dysfunction remains unexplored. The study aimed to explore the potential protective effects of NAR in CI/R injury-induced cognitive dysfunction and underlying mechanism. The rats were exposed to transient middle cerebral artery occlusion (MCAO) and then treated with distilled water or NAR (50 or 100 mg/kg/day, p.o.) for 30 days. The Y-maze test, Novel object recognition test and Morris water maze test were performed to assess cognitive function. The levels of oxidative stress and inflammatory cytokines were measured by ELISA. The expressions of BDNF/TrkB signaling were detected by Western blot. NAR prevented cognitive impairment in MCAO-induced CI/R injury rats. Moreover, NAR inhibited oxidative stress (reduced levels of malondialdehyde and 4-hydroxynonenal, increased activities of superoxide dismutase and Glutathione peroxidase) and inflammatory cytokines (reduced levels of tumor necrosis factor-α, Interleukin-1ß and Interleukin-6), up-regulated the expressions of BDNF and p-TrkB in hippocampus of MCAO-induced CI/R rats. NAR ameliorated cognitive dysfunction of CI/R rats via inhibiting oxidative stress, reducing inflammatory response, and up-regulating BDNF/TrkB signaling pathways in the hippocampus.

Nasopharyngeal Angiofibroma in an Adult Male: A Case Report and Review of the Literature.

A 32-year-old male presented with recurrent bilateral epistaxis and nasal obstruction, leading to a rare diagnosis of nasopharyngeal angiofibroma. Although primarily observed in adolescents, this case underscores its presence in older populations. The patient underwent a successful endoscopic resection, contributing to the scant documented instances of such cases in adult U.S. males.

Influence of samarium modification on the phase-change performance and phase structure of tin antimonide.

This work presents the optimization of the crystallization behavior and reliability of Sn15Sb85thin films by doping Sm element. The phase transition behaviors induced by thermal were investigated byin situresistance measurement. With the addition of Sm element, Sn15Sb85film exhibits the superior crystallization temperature (232 °C) and data conservation (172.32 °C for 10 years), larger activation energy of crystallization (4.91 eV) and crystalline resistance (∼103Ω), which contributes to the increased thermal stability of the amorphous state and decrease in the programming energy. The Sm-doping can broaden the energy band gap from 0.55 to 1.07 eV. The amorphous Sm and Sn compositions could retard grain growth and refine grain size from 21.13 to 11.13 nm, combining with x-ray diffraction and x-ray photoelectron spectroscopy. The surface morphology of Sn15Sb85film becomes smoother after Sm doping as determined by atomic force microscopy images, resulting in the improved interfacial reliability. Phase change memory devices based on Sm0.095(Sn15Sb85)0.905films can successfully achieve the complete SET and RESET reversible operation process with high operating speed (200 ns) and low power consumption (1.6 × 10-10J). The results suggest that doping the proper concentration of Sm element will be an effectual solution to adapt and optimize the crystallization properties of Sn15Sb85phase change material.

Unhealthy Eating Behaviors During Pregnancy and Gestational Weight Gain - Huai'an City, Jiangsu Province, China, 2020-2021.

What is already known about this topic?: Maintaining a healthy diet and appropriate weight during pregnancy is crucial for both the expectant mother and the fetus. Unhealthy eating behaviors (UEBs) such as eating out frequently are becoming increasingly prevalent across the globe. However, there is a dearth of research investigating the relationship between UEBs and gestational weight gain (GWG) specifically in the context of Chinese women. What is added by this report?: The study revealed that a majority of pregnant women reported experiencing one or more UEBs such as eating fast, eating three meals irregularly, eating away from home, and skipping breakfast. A positive association was also observed between the number of UEBs and elevated odds of experiencing excessive GWG. What are the implications for public health practice?: The uptake of emerging UEBs is prevalent among pregnant women in China. It is recommended that healthy eating behavior become the focal point of gestational weight management in clinical practice. Moreover, preconception care should take into account customized health education and promotion programs.

A novel multi-frame wavelet generative adversarial network for scattering reconstruction of structured illumination microscopy.

Objective. Structured illumination microscopy (SIM) is widely used in various fields of life science research. In clinical practice, it has low phototoxicity, fast imaging speed and no special fluorescent markers. However, SIM is still affected by the scattering medium of biological tissues, resulting in insufficient resolution of the obtained images, which limits the development of life sciences. A novel multi-frame wavelet generation adversarial network (MWGAN) is proposed to improve the scattering reconstruction capability of SIM.Approach. MWGAN is based on two components derived from the original image. A generative adversarial network constructed by wavelet transform is trained to reconstruct some complex details in the cell structure. Multi-frame adversarial network is used to obtain the inter-frame information of the image and use the complementary information of the before and after frames to improve the quality of the model reconstruction.Results. To demonstrate the robustness of MWGAN, multiple low-quality SIM image datasets are tested. Compared with the state-of-the-art methods, the proposed method achieves superior performance in both of the subjective and objective evaluation.Conclusion. MWGAN is effective for improving the clarity of SIM images. Meanwhile, the SIM images reconstructed by multiple frames improve the reconstruction quality of complex regions and allow clearer and dynamic observation of cellular functions.

Autoantibodies Targeting Unknown Epitope Autoimmune Encephalitis and the Effect of Modified Electroconvulsive Therapy: Report of Three Cases.

Objective: Generally autoimmune encephalitis (AE) cases present with central nervous system symptoms. Many types of autoantibodies are associated with autoimmune encephalitis, with anti-N-methyl-D-aspartate receptor being the most commonly reported. However, autoimmune encephalitis cases with autoantibodies targeting unknown epitopes are increasingly recognized. This article aims to summarize the clinical experience and assess the feasibility of modified electroconvulsive therapy (MECT) as an adjunctive treatment method for autoimmune encephalitis patients with poor response to first-line immunotherapy and mainly displaying psychiatric symptoms. Methods: This work reports three cases of which two have been diagnosed as autoantibodies targeting unknown epitope autoimmune encephalitis while one has been diagnosed as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and all were effectively treated with MECT. Results: All three cases that otherwise failed to respond to standard immunotherapy for controlling psychiatric symptoms exhibited excellent clinical outcomes following MECT. The underlying mechanism of action of MECT is unclear and whether such an effect involves a neurotransmitter rebalance in the brain remains uncertain. At present, we have observed only a small number of clinical cases, warranting further research among a larger number of clinical cases and more systematic multicenter retrospective analysis. Conclusions: It should be noted that, while our experience supports the utility of MECT in the treatment of certain cases of AE, this option should be regarded as an adjuvant therapy after standard immunosuppressive therapy. Clinicians must be aware that patients should be provided with psychiatric or neurological services for timely diagnosis along with timely and appropriate treatment.

Parental control and adolescent internet addiction: the moderating effect of parent-child relationships.

Introduction: The present study investigated how maternal and paternal controls, including behavioral and psychological controls, predict adolescent Internet addiction, as well as the potential moderating effects of adolescent gender and parent-child relationships on the predictions. Methods: Data were collected from 1,974 Chinese adolescents (age range = 14-22; mean = 16.47; SD = 0.87; 1,099 girls) in Guizhou Province, mainland China in November 2021. Internet addiction was measured using the ten-item Internet Addiction Test developed by Kimberly Young, and Parental control and parent-child relationships were measured by the respective subscales derived from the validated Chinese Parent-Child Subsystem Quality Scale. Results: Hierarchical regression analyses revealed that after the covariates were statistically controlled, both parents' behavioral controls showed significant negative predictions on adolescent Internet addiction, while their psychological control tended to positively predict Internet addiction among adolescents, although the effect was only marginal. In addition, the impacts of maternal and paternal controls were equal, and such impacts did not vary between sons and daughters. While adolescent gender was not a significant moderator, the parent-child relationship quality significantly moderated the effects of paternal behavioral control, paternal psychological control, and maternal psychological control on adolescents' Internet addiction. Specifically, the prediction of paternal behavioral control was stronger while the effect of paternal and maternal psychological control was weaker among adolescents with a positive father-child relationship than those with a moderate or poor father-child relationship. Discussion: These findings indicate the protective function of parents' behavioral control and the negative impact of psychological control on the development of adolescent Internet addiction. Further, a positive relationship between the father and the adolescent can strengthen the positive effect of paternal behavioral control and mitigate the negative effects of both parents' psychological controls.

Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability.

The clinical application of EDV, a potent antioxidant drug approved for amyotrophic lateral sclerosis (ALS), is limited by its short biological half-life and poor water solubility necessitating hospitalization during intravenous infusion. Nanotechnology-based drug delivery constitutes a powerful tool through inferring drug stability and targeted drug delivery improving drug bioavailability at the diseased site. Nose-to-brain drug delivery offers direct access to the brain bypassing the blood brain barrier and reducing systemic biodistribution. In this study, we designed EDV-loaded poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles (NP-EDV) for intranasal administration. NPs were formulated by the nanoprecipitation method. Morphology, EDV loading, physicochemical properties, shelf-life stability, in vitro release and pharmacokinetic assessment in mice were conducted. EDV was efficiently loaded into ∼90 nm NPs, stable up to 30 days of storage, at ∼3% drug loading. NP-EDV reduced H2O2-induced oxidative stress toxicity in mouse microglial cell line BV-2. Optical imaging and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed that intranasal delivery of NP-EDV offered higher and more sustained brain uptake of EDV compared to intravenous administration. This study is the first of its kind to develop an ALS drug in a nanoparticulate formulation for nose-to-brain delivery raising hope to ALS patients where currently treatment options are limited to two clinically approved drugs only.