The RNA helicase Ddx52 functions as a growth switch in juvenile zebrafish.

Vertebrate animals usually display robust growth trajectories during juvenile stages, and reversible suspension of this growth momentum by a single genetic determinant has not been reported. Here, we report a single genetic factor that is essential for juvenile growth in zebrafish. Using a forward genetic screen, we recovered a temperature-sensitive allele, pan (after Peter Pan), that suspends whole-organism growth at juvenile stages. Remarkably, even after growth is halted for a full 8-week period, pan mutants are able to resume a robust growth trajectory after release from the restrictive temperature, eventually growing into fertile adults without apparent adverse phenotypes. Positional cloning and complementation assays revealed that pan encodes a probable ATP-dependent RNA helicase (DEAD-Box Helicase 52; ddx52) that maintains the level of 47S precursor ribosomal RNA. Furthermore, genetic silencing of ddx52 and pharmacological inhibition of bulk RNA transcription similarly suspend the growth of flies, zebrafish and mice. Our findings reveal evidence that safe, reversible pauses of juvenile growth can be mediated by targeting the activity of a single gene, and that its pausing mechanism has high evolutionary conservation.

Increased Expression of KNa1.2 Channel by MAPK Pathway Regulates Neuronal Activity Following Traumatic Brain Injury.

Recent studies have indicated that functional abnormalities in the KNa1.2 channel are linked to epileptic encephalopathies. However, the role of KNa1.2 channel in traumatic brain injury (TBI) remains limited. We collected brain tissue from the TBI mice and patients with post-traumatic epilepsy (PTE) to determine changes in KNa1.2 channel following TBI. We also investigated whether the MAPK pathway, which was activated by the released cytokines after injury, regulated KNa1.2 channel in in vitro. Finally, to elucidate the physiological significance of KNa1.2 channel in neuronal excitability, we utilized the null mutant-Kcnt2-/- mice and compared their behavior patterns, seizure susceptibility, and neuronal firing properties to wild type (WT) mice. TBI was induced in both Kcnt2-/- and WT mice to investigate any differences between the two groups under pathological condition. Our findings revealed that the expression of KNa1.2 channel was notably increased only during the acute phase following TBI, while no significant elevation was observed during the late phase. Furthermore, we identified the released cytokines and activated MAPK pathway in the neurons after TBI and confirmed that KNa1.2 channel was enhanced by the MAPK pathway via stimulation of TNF-α. Subsequently, compared to WT mice, neurons from Kcnt2-/- mice showed increased neuronal excitability and Kcnt2-/- mice displayed motor deficits and enhanced seizure susceptibility, which suggested that KNa1.2 channel may be neuroprotective. Therefore, this study suggests that enhanced KNa1.2 channel, facilitated by the inflammatory response, may exert a protective role in an acute phase of the TBI model.

Wind-Speed-Adaptive Resonant Piezoelectric Energy Harvester for Offshore Wind Energy Collection.

This paper proposes a wind-speed-adaptive resonant piezoelectric energy harvester for offshore wind energy collection (A-PEH). The device incorporates a coil spring structure, which sets the maximum threshold of the output rotational frequency, allowing the A-PEH to maintain a stable output rotational frequency over a broader range of wind speeds. When the maximum output excitation frequency of the A-PEH falls within the sub-resonant range of the piezoelectric beam, the device becomes wind-speed-adaptive, enabling it to operate in a sub-resonant state over a wider range of wind speeds. Offshore winds exhibit an annual average speed exceeding 5.5 m/s with significant variability. Drawing from the characteristics of offshore winds, a prototype of the A-PEH was fabricated. The experimental findings reveal that in wind speed environments, the device has a startup wind speed of 4 m/s, and operates in a sub-resonant state when the wind speed exceeds 6 m/s. At this point, the A-PEH achieves a maximum open-circuit voltage of 40 V and an average power of 0.64 mW. The wind-speed-adaptive capability of the A-PEH enhances its ability to harness offshore wind energy, showcasing its potential applications in offshore wind environments.

Eating disorders symptoms and depressive symptoms in Chinese Tibetan University students: a network analysis.

BACKGROUND: Depression is being increasingly acknowledged as a global public health concern, and following this trend, attention towards eating disorders (EDs) has surged within China's national consciousness. EDs symptoms frequently coexist with various mental health conditions, including depression. However, research focusing on EDs symptoms and depressive symptoms among Tibetan students in China remains scant. This study employs network analysis to estimate the relational network between EDs and depressive symptoms. METHODS: Tibetan (n = 2,582) and Han (n = 1,743) students from two universities in the Xizang Autonomous Region, China, completed the Eating Attitude Test-26 (EAT-26) and the Patient Health Questionnaire-9 (PHQ-9). We estimated the network structure of EDs symptoms and depressive symptoms, identified central and bridge symptoms, and examined whether network characteristics differed by gender and ethnic. RESULTS: The core symptoms identified within this study were Calorie_awareness, Desire_to_thin and Fatigue. Conversely, bridge symptoms included Appetite, Suicide, Anhedonia, Guilty, Body_fat_awareness, and Food_preoccupation. The study also revealed no significant gender differences within the network model. However, disparities among ethnic groups were observed within the network structure. CONCLUSIONS: Our study examined the correlation between EDs symptoms and depressive symptoms in Tibetan college students. Focusing on the individual's quest for the perfect body shape and some Tibetan students' appetite problems - potentially stemming from transitioning to a new university environment, adapting to the school canteen's diet, or being away from their hometown - could aid in the prevention and management of EDs and depression symptoms. It could reduce the incidence of complications by helping students maintain good physical and mental health. Concurrently, our research provides insights into the relatively higher levels of depression triggered by the unique plateau environment.

Evaluating Effectiveness and Safety in Chronic Kidney Disease with Atrial Flutter Using an Anticoagulation Strategy.

Background and Objectives: Recent randomized trials of oral antithrombotic drugs with atrial flutter (AFL) excluded patients with renal impairment because of their increased risk of bleeding. To date, no relevant studies have assessed the effectiveness and safety of different antithrombotic drugs in chronic kidney disease (CKD) patients with AFL. This cohort study evaluated the effectiveness and safety of different antithrombotic drugs in CKD patients with AFL. This study also investigated the risk of cardiovascular events from antithrombotic drugs through different risk profiles of stroke stratified by the CHA2DS2-VASc score. Materials and Methods: This cohort study was performed in patients with AFL and CKD who were extracted from the National Health Insurance (NHI) Database in Taiwan. Oral antithrombotic therapy (oral anticoagulants (OAC) or antiplatelets (APT)) was administered to patients who had been diagnosed with AFL after being diagnosed with CKD between 2011 and 2015. Primary outcomes, including ischemic stroke, systemic embolism, and composite of stroke, and secondary outcomes, including major adverse cardiac events (MACEs), major bleeding, all-cause mortality, and cardiovascular-related death, were examined. Results: A total of 2468 patients were included in this study. The results showed no statistically significant differences in the risk of primary outcomes. For the secondary outcomes, there were also no statistically significant differences in the risk of MACEs and major bleeding. However, the pooled results indicated that the hazard ratio (HR) for all-cause mortality with OAC was 0.24 (95% confidence interval (CI) = 0.10-0.55) compared with combination therapy, and the HR for APT compared with OAC was 2.86 (95% CI = 1.48-5.53). Conclusions: In the studied population, OAC or APT alone were proved equally effective for stroke prophylaxis. Furthermore, OAC might reduce the all-cause mortality rate compared with APT and should be considered as the first choice of oral antithrombotic drugs in patients with AFL and CKD.

Developing in vitro assays to quantitatively evaluate the interactions of dressings with wounds.

Evaluating interactions between dressing and wound is important for understanding wound management. This study quantitatively compared four polyurethane foam-based wound dressings for their absorption profile, cell penetration, and adherence using two novel in vitro assays. The dressing with uniform pore sizes varying from 25~75 µm showed the highest absorption of both culture media and serum. The same dressing showed a 1.2- to 3.6-fold lower cell adherence (3 hours) than the other dressings, and ~20-fold lower cell penetration (5 days) than dressings with pore sizes varying from 55 to 343 µm. Additionally, cell and dressing interactions using a 3-dimensional wound healing assay showed that the dressings with the smallest pore size of 25~75 µm maintained the highest cell viability (76.3%) and promoted cell migration into the wound site. This data suggest that polyurethane foam dressing with smaller and evenly distributed pores promotes wound healing with less cellular adhesion and penetration.

Enterobius vermicularis infection: prevalence and risk factors among preschool children in kindergarten in the capital area, Republic of the Marshall Islands.

BACKGROUND: Enterobius vermicularis (pinworm) is one of the most common human parasitic helminths, and children are the most susceptible group. Some behavioral and environmental factors may facilitate pinworm infection. In the Republic of the Marshall Islands (RMI), the status of pinworm infections among children remains unknown. METHODS: In Majuro City, there are 14 kindergartens with a total of 635 preschool children (PSC) whose age range of 5~6 years. The present investigation attempted to determine the pinworm prevalence and associated risk factors as well as investigate whether eggs contaminated the clothes of PSC or the ground and tables in classrooms of 14 kindergartens. Informed consent form and a self-administered questionnaire were given to parents prior to pinworm screening. Perianal specimens were collected by an adhesive scotch tape method, and clothing of belly and hip sites and the ground and tables of the classrooms were inspected using a cellophane tape method to detect any eggs contamination. RESULTS: In total, 392 PSC (5.28 ± 0.56 yrs. old) participated in this project. The overall prevalence of pinworm infection was 22.4% (88/392). Boys (24.5%) had higher prevalence than girls (20.31%) (p = 0.32). PSC aged > 5 years (32.77%) showed a significantly higher prevalence than those aged ≤5 years (17.95%) (p = 0.01). A univariate analysis indicated that PSC who lived in urban areas (22.95%) had a higher prevalence than those who lived in rural areas (20.69%) (p = 0.69). The employment status of the parents showed no association with the pinworm infection rate (p > 0.05). A logistic regression analysis indicated that "having an older sister" produced a higher risk of acquiring pinworm infection for PSC compared to those who did not have an older sister (OR = 2.02; 95%CI = 1.05~3.88; p = 0.04). No significant association between various other risk factors and pinworm infection was found (p > 0.05). Also, no eggs contamination was found on the clothes of the belly and hip sites or on the ground and tables in the 14 kindergartens. CONCLUSIONS: Mass screening and treatment of infected PSC are important measures in pinworm control in the RMI.

Docetaxel-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles in human breast cancer and human cervical cancer therapy.

Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and 'self-controlled' drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.

Chondrocytes damage induced by T-2 toxin via Wnt/ß-catenin signaling pathway is involved in the pathogenesis of an endemic osteochondropathy, Kashin-Beck disease.

Kashin-Beck disease (KBD), an endemic osteochondropathy, is characterized by cartilage degeneration which is caused by abnormal catabolism in the extracellular matrix (ECM). In this study, we investigated the expression of the Wnt/ß-catenin signaling pathway in KBD pathogenesis. Among the proteins involved in the Wnt/ß-catenin signaling pathway, WNT-3A, FZD1, SOX9, and ß-catenin were up-regulated, while FRZB was down-regulated in KBD cartilage. C28/I2 cells were evaluated for cell viability using the MTT assay after exposure to T-2 toxin, a suspicious environmental pathogenic factors of KBD. C28/I2 cells were treated with different intervening concentrations (0.001µg/mL,0.005µg/mL and 0.01µg/mL) of T-2 toxin for 24h. The expression of FZD1 and CTNNB1 (i.e.,ß-catenin) was significantly reduced and SOX9 expression was significantly increased in chondrocytes after treatment with different intervening concentrations of T-2 toxin. Our results indicate that alterations in the Wnt/ß-catenin signaling pathway in articular cartilage play an important role in the onset and pathogenesis of KBD.

Children's exposure to secondhand smoke at home before and after smoke-free legislation in Taiwan.

INTRODUCTION: In January 2009, Taiwan broadened smoke-free legislation, requiring mass transportation systems, indoor public areas and indoor workplaces with 3 or more people, to become smoke-free. We investigated the secondhand smoke (SHS) exposure at home for children aged 3-11 years in Taiwan before and after the implantation of the legislation. METHODS: We studied 7911 children from the 2005, 2009 and 2013 National Health Interview Surveys (cross-sectional, nationally representative household surveys). Logistic regression modelling estimated adjusted ORs (AOR) and 95% CIs for children's SHS exposure at home in 2009 and 2013 (2005 as reference) for the overall sample and for each category of household socioeconomic status (SES) and household composition. RESULTS: Prevalence of children SHS exposure at home decreased from 51% (2005) to 32% (2009) and 28% (2013). Compared to 2005, children in 2009 and 2013 had lower likelihoods of SHS exposure at home with AOR of 0.45 (95% CI 0.41 to 0.51) and 0.41 (95% CI 0.36 to 0.46), respectively. All children had reduced SHS exposure at home after the legislation, irrespective of household SES and compositions. Low household income, low parental education level, living with grandparents or living with other adults was individually associated with increased SHS exposure. DISCUSSION: The proportion of children exposed to SHS at home in Taiwan declined substantially from 2005 to 2009 after smoke-free legislation, and fell further by 2013, irrespective of SES and household compositions. Still, inequality in SHS exposure at home by SES and household composition warrants future research.

Roles of Glycoproteins in the Diagnosis and Differential Diagnosis of Chronic and Latent Keshan Disease.

We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 CKD, 50 LKD patients and 54 normal individuals. Saliva and serum lectin microarrays and saliva and serum microarrays were used to screen and verify the differences in the levels of lectin among the three groups. In the male saliva lectin microarray, Solanum tuberosum (potato) lectin (STL) and other 9 lectins showed differences between CKD and normal; STL and other 9 lectins showed differences between LKD and normal; Aleuria aurantia lectin (AAL) and other 15 lectins showed differences between CKD and LKD. In the female saliva microarray, Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) and other 9 lectins showed differences between CKD and normal; STL and other 7 lectins showed differences between LKD and normal; Maackia amurensis lectin I (MAL-I) and Triticum vulgaris (WGA) showed difference between CKD and LKD. In the male serum lectin microarray, Psophocarpus tetragonolobus lectin I (PTL-I) and other 16 lectins showed differences between CKD and normal; Ulexeuropaeus agglutinin I (UEA-I) and other 9 lectins showed differences between LKD and normal; AAL and other 13 lectins showed differences between CKD and LKD. In the female serum lectin microarray, WGA and other 13 lectins showed differences between CKD and normal; Euonymus europaeus lectin (EEL) and other 6 lectins showed differences between LKD and normal; MAL-I and other 14 lectins showed differences between CKD and LKD. Carbohydrate chain GlcNAc and α-Gal may play crucial roles in the pathogenesis of KD. STL may be considered the diagnostic biomarker for male CKD and LKD, while WGA may be useful in distinguishing between the two stages. STL may be considered the diagnostic biomarker for female LKD.

[Self-Awareness of Disease Stigma: Reflections of Healthcare Professionals].

People who suffer from disease frequently experience disease-related stigmas. Stigma presents in daily life during normal human interactions. The stereotypes promoted by the media often impact public opinion significantly. Moreover, healthcare professionals may exacerbate stigmatization due to their misunderstanding of patients and their disease issues. Therefore, the reflection on stigma of healthcare professionals cannot be ignored. The present article illustrates the issue of stigmas held by healthcare professionals, their related stigmas, and their self-awareness. It is hoped that all healthcare professionals may cooperate to develop an anti-stigma strategy and to become true spokespersons for their patients.

Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-ß and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.

Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection.

Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP.

An eight-year epidemiologic study based on baculovirus-expressed type-specific spike proteins for the differentiation of type I and II feline coronavirus infections.

BACKGROUND: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). FCoVs are divided into two serotypes with markedly different infection rates among cat populations around the world. A baculovirus-expressed type-specific domain of the spike proteins of FCoV was used to survey the infection of the two viruses over the past eight years in Taiwan. RESULTS: An immunofluorescence assay based on cells infected with the recombinant viruses that was capable of distinguishing between the two types of viral infection was established. A total of 833 cases from a teaching hospital was surveyed for prevalence of different FCoV infections. Infection of the type I FCoV was dominant, with a seropositive rate of 70.4%, whereas 3.5% of cats were infected with the type II FCoV. In most cases, results derived from serotyping and genotyping were highly agreeable. However, 16.7% (4/24) FIP cats and 9.8% (6/61) clinically healthy cats were found to possess antibodies against both viruses. Moreover, most of the cats (84.6%, 22/26) infected with a genotypic untypable virus bearing a type I FCoV antibody. CONCLUSION: A relatively simple serotyping method to distinguish between two types of FCoV infection was developed. Based on this method, two types of FCoV infection in Taiwan was first carried out. Type I FCoV was found to be predominant compared with type II virus. Results derived from serotyping and genotyping support our current understanding of evolution of disease-related FCoV and transmission of FIP.

Nanomechanics insights into the performance of healthy and osteoporotic bones.

In situ nanoscopic observations of healthy and osteoporotic bone nanopillars under compression were performed. The structural-mechanical property relationship at the atomic scale suggests that cortical bone performance is correlated to the feature, arrangement, movement, distortion, and fracture of hydroxyapatite nanocrystals. Healthy bone comprising tightly bound mineral nanocrystals shows high structural stability with nanoscopic lattice distortions and dislocation activities. On the other hand, osteoporotic bone exhibits brittleness owing to the movements of dispersed minerals in and intergranular fracture along a weak organic matrix.

Wind-Wave Synergistic Triboelectric Nanogenerator: Performance Evaluation Test and Potential Applications in Offshore Areas.

Triboelectric nanogenerators (TENGs) can effectively collect low-frequency, disordered mechanical energy and are therefore widely studied in the field of ocean energy collection. Most of the rotary TENGs studied so far tend to have insufficient rotation, resulting in slow charge transfer rates in low-frequency ocean environments. For this reason, in this paper, we propose a wind-wave synergistic triboelectric nanogenerator (WWS-TENG). It is different from the traditional rotary TENGs based on free-standing mode in that its power generation unit has two types of rotors, and the two rotors rotate in opposite directions under the action of wind energy and wave energy, respectively. This type of exercise can more effectively collect energy. The WWS-TENG has demonstrated excellent performance in sea wind and wave energy harvesting. In the simulated ocean environment, the peak power can reach 13.5 mW under simulated wind-wave superposition excitation; the output of the WWS-TENG increased by 49% compared to single-wave power generation. The WWS-TENG proposal provides a novel means of developing marine renewable energy, and it also demonstrates broad application potential in the field of the self-powered marine Internet of Things (IoT).

Wind Aggregation Enhanced Triboelectric-Electromagnetic Hybrid Generator with Slit Effect.

It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.

Inhibiting acid-sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis.

BACKGROUND: Epilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease-modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid-sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+ ]i . However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown. METHODS: In our study, we explored the changes in ferroptosis-related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products-malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug-resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis-related indices in the in vitro 0-Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons. RESULTS: Our study first reported significant changes in ferroptosis-related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4-HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer-1, alleviate oxidative stress response, and decrease [Ca2+ ]i overload by inhibiting the overexpressed ASIC1a in the in vitro epilepsy model induced by 0-Mg2+ . CONCLUSION: Inhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+ ]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs.

The Impact of Problematic Smartphone Use on Sleep Quality Among Chinese Young Adults: Investigating Anxiety and Depression as Mediators in a Three-Wave Longitudinal Study.

Background: Sleep disorders are a significant health issue that urgently needs to be addressed among undergraduate students, and one of the potential underlying problems could be problematic smartphone use (PSU). This study aimed to clarify the relationship between PSU and poor sleep quality by investigating the independent and serial mediating roles of anxiety and depressive symptoms in a population of university students in Tibet, China. Methods: A total of 2993 Tibetan college students completed three waves of data surveys, with all participants completing questionnaires on PSU, anxiety, depressive symptoms, and sleep quality (Time 1 (T1) -Time 3 (T3)). Bootstrapped mediation analysis was used to explore the mediating role of anxiety and depressive symptoms in the longitudinal relationship between PSU and sleep quality. Results: Both direct and indirect effects of PSU on poor sleep quality were found. PSU (T1) can had not only a direct negative influence on poor sleep quality (T3) among young adults (direct effect = 0.021, 95% CI = 0.010-0.033) but also an indirect negative impact via three pathways: the independent mediating effect of anxiety symptoms (T2) (indirect effect 1 = 0.003, 95% CI = 0.001-0.006), the independent mediating effect of depressive symptoms (T2) (indirect effect 2 = 0.004, 95% CI = 0.002-0.006), and the serial mediating effects of anxiety (T2) and depressive symptoms (T2) (indirect effect 3 = 0.008, 95% CI=0.005-0.011). Conclusion: These findings highlight the role of anxiety and depression symptoms as joint mediating factors in the relationship between PSU and sleep disturbances. Interventions focused on improving sleep that incorporate behavioural measures could benefit from treatment approaches targeting mental disorders.