Fullerenols Ameliorate Social Deficiency and Rescue Cognitive Dysfunction of BTBR T+Itpr3tf/J Autistic-Like Mice.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments. Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining. Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment. Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.

Understanding the link between different types of maternal diabetes and the onset of autism spectrum disorders.

Autism spectrum disorders (ASD) encompass a collection of neurodevelopmental disorders that exhibit impaired social interactions and repetitive stereotypic behaviors. Although the exact cause of these disorders remains unknown, it is widely accepted that both genetic and environmental factors contribute to their onset and progression. Recent studies have highlighted the potential negative impact of maternal diabetes on embryonic neurodevelopment, suggesting that intrauterine hyperglycemia could pose an additional risk to early brain development and contribute to the development of ASD. This paper presents a comprehensive analysis of the current research on the relationship between various forms of maternal diabetes, such as type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus, and the likelihood of ASD in offspring. The study elucidates the potential mechanisms through which maternal hyperglycemia affects fetal development, involving metabolic hormones, immune dysregulation, heightened oxidative stress, and epigenetic alterations. The findings of this review offer valuable insights for potential preventive measures and evidence-based interventions targeting ASD.

Curcumin-loaded mesoporous polydopamine nanoparticles modified by quaternized chitosan against bacterial infection through synergistic effect.

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.

Finite Element Analysis of Different Carbon Fiber Reinforced Polyetheretherketone Dental Implants in Implant-supported Fixed Denture.

OBJECTIVES: The purpose of this study is to determine the feasibility of polyetheretherketone-based dental implants, and analyze the stress and strain around different kinds of dental implants by finite element analysis. METHODS: The radiographic data was disposed to models in Mimics 19.0. 3D models of implants, crowns and jawbones were established and combined in SolidWorks 2018. Appling axial and oblique loads of 100 N, cloud pictures were exported in Ansys Workbench 18.0 to calculate and analyze the stress and strain in and around different implants. RESULTS: Oblique load tended to deliver more stress to bone tissue than axial load. The uniformity of stress distribution was the best for 30% short carbon fiber reinforced polyetheretherketone implants at axial and buccolingual directions. Stress shielding phenomenon occurred at the neck of 60% continuous carbon fiber reinforced polyetheretherketone and titanium implants. Stress concentration appeared in PEEK implants and the load of bone tissue would aggravate. CONCLUSIONS: 30% short carbon fiber reinforced polyetheretherketone implants demonstrate a more uniform stress distribution in bone-implant contact and surrounding bone than titanium. Stress shielding and stress concentration may be avoided in bone-implant interface and bone tissue. Bone disuse-atrophy may be inhibited in PEEK-based implants.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.

Clinical factors influencing the effectiveness of microplasma fractional radiofrequency treatment for atrophic acne scars: A retrospective analysis.

BACKGROUND: Microplasma fractional radiofrequency (MP FRF) technology has been increasingly used for acne scars. Nevertheless, little evidence has analyzed the factors influencing its effectiveness before and during treatment. AIMS: To evaluate the clinical factors affecting the effectiveness of MP FRF therapy for atrophic acne scars. METHODS: We analyzed retrospectively the clinical data of 79 acne scar patients treated with MP FRF technology. The outcome of interest included the effectiveness and adverse events after MP FRF treatment. Multivariable logistic regression was utilized to evaluate clinical factors associated with effectiveness after the initial session. RESULTS: All patients received 115 sessions of MP FRF therapy (average: 1.5 sessions). Twenty-eight (35.4%) patients improved moderately to excellently after one session. We found that the severe grade before treatment was negatively correlated with the effectiveness according to Goodman-Baron qualitative scores (OR = 0.02, 95% CI [0.001, 0.37], p = 0.009). The presence of icepick scars was also a negative correlation factor for the effectiveness (OR = 0.06, 95% CI [0.004, 1.00], p = 0.049). Furthermore, after excluding the effects of icepick scars and Goodman-Baron scores before treatment, ECCA scores were also correlated with effectiveness (OR = 1.04, 95% CI [1.01, 1.06], p = 0.009). CONCLUSION: MP FRF therapy was effective in treating atrophic acne scars with no permanent adverse events. The severity of Goodman-Baron qualitative scores and icepick scars were independent clinical factors affecting effectiveness, suggesting the possible requirement for additional treatments other than MP FRF for severe acne scars and icepick scars.

Safety and efficacy of bempedoic acid among patients with statin intolerance and those without: A meta-analysis and a systematic randomized controlled trial review.

OBJECTIVE: Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness. METHODS: A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated. RESULTS: Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27). CONCLUSIONS: In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.

Macrophages in the process of osseointegration around the implant and their regulatory strategies.

PURPOSE/AIM OF THE STUDY: To summarize and discuss macrophage properties and their roles and mechanisms in the process of osseointegration in a comprehensive manner, and to provide theoretical support and research direction for future implant surface modification efforts. MATERIALS AND METHODS: Based on relevant high-quality articles, this article reviews the role of macrophages in various stages of osseointegration and methods of implant modification. RESULTS AND CONCLUSIONS: Macrophages not only promote osseointegration through immunomodulation, but also secrete a variety of cytokines, which play a key role in the angiogenic and osteogenic phases of osseointegration. There is no "good" or "bad" difference between the M1 and M2 phenotypes of macrophages, but their timely presence and sequential switching play a crucial role in implant osseointegration. In the implant surface modification strategy, the induction of sequential activation of the M1 and M2 phenotypes of macrophages is a brighter prospect for implant surface modification than inducing the polarization of macrophages to the M1 or M2 phenotypes individually, which is a promising pathway to enhance the effect of osseointegration and increase the success rate of implant surgery.

The Chinese Parenting Stress Scale for Preschoolers' Parents: Development and Initial Validation.

Parenting stress is the experience of discomfort or distress that results from the demands associated with the role of parenting. Although there are numerous parenting stress scales, relatively few scales have been developed with consideration of the Chinese cultural context. This study aimed to develop and validate the Chinese Parenting Stress Scale (CPSS) with a multidimensional and hierarchical structure for Mainland Chinese preschoolers' parents (N = 1,427, Mage = 35.63 years, SD = 4.69). In Study 1, a theoretical model and an initial 118 items were developed, drawing on prior research and existing measures of parenting stress. Exploratory factor analysis yielded 15 first-order factors with 60 items. In Study 2, confirmatory factor analyses supported a higher order solution consisting of 15 first-order factors covering four domains: Child Development (12 items), Difficult Child (16 items), Parent-Child Interaction (12 items), and Parent's Readjustment to Life (20 items). Measurement invariance indicated no gender differences between parents for the scale scores. The convergent, discriminant, and criteria validity of the CPSS scores was supported by its association with related variables in the expected directions. Moreover, the CPSS scores added significant incremental variance in predicting somatization, anxiety, and child's emotional symptoms more so than the Parenting Stress Index-Short Form-15. The CPSS total and subscale scores all had acceptable Cronbach's αs in both samples. The overall findings support the CPSS as a psychometrically sound tool.

Parenting stress and Chinese preschoolers' approaches to learning: a moderated mediation model of authoritative parenting and household residency.

According to the family stress model, this study examined the relationship between parenting stress and preschoolers' approaches to learning (ATL) in China, as well as the mediating effect of authoritative parenting and the moderating effect of household residency (migrant and native). A survey of 5,047 preschoolers' parents (2,186 natives and 2,861 migrants) supports the proposed moderated mediation model. The results showed that after controlling for gender and age, parenting stress affected preschoolers' development of ATL negatively. Authoritative parenting mediates the relationship between parenting stress and preschoolers' ATL. Further, household residency moderated the relationship between authoritative parenting and preschoolers' ATL. The findings of this study suggest that high levels of parenting stress are detrimental to the development of preschoolers' ATL. And parents with low parenting stress are more likely to adopt authoritative parenting, which in turn fosters preschoolers' ATL. In addition, native families' authoritative parenting style are more conducive to fostering preschoolers' ATL than migrant families. Finally, this study contributes to previous research by examining the mechanisms of parenting stress on preschoolers' ATL and provides support for the extension of the family stress model. Importantly, it also informs efforts to improve ATL among preschoolers in Chinese migrant and native families.

Protein-polysaccharide-based delivery systems for enhancing the bioavailability of curcumin: A review.

In recent years, a wide attention has been paid to curcumin in medicine due to its excellent physiological activities, including anti-inflammatory, antioxidant, antibacterial, and nerve damage repair. However, the low solubility, poor stability, and rapid metabolism of curcumin make its bioavailability low, which affects its development and application. As a unique biopolymer structure, protein-polysaccharide (PRO-POL)-based delivery system has the advantages of low toxicity, biocompatibility, biodegradability, and delayed release. Many scholars have investigated PRO-POL -based delivery systems to improve the bioavailability of curcumin. In this paper, we focus on the interactions between different proteins (e.g. casein, whey protein, soybean protein isolate, pea protein, zein, etc.) and polysaccharides (chitosan, sodium alginate, hyaluronic acid, pectin, etc.) and their effects on complexes diameter, surface charge, encapsulation drive, and release characteristics. The mechanism of the PRO-POL-based delivery system to enhance the bioavailability of curcumin is highlighted. In addition, the application of PRO-POL complexes loaded with curcumin is summarized, aiming to provide a reference for the construction and application of PRO-POL delivery systems.

Electrosynthesis of a nylon-6 precursor from cyclohexanone and nitrite under ambient conditions.

Cyclohexanone oxime, an important nylon-6 precursor, is conventionally synthesized through cyclohexanone-hydroxylamine (NH2OH) and cyclohexanone ammoxidation methodologies. These strategies require complicated procedures, high temperatures, noble metal catalysts, and toxic SO2 or H2O2 usage. Here, we report a one-step electrochemical strategy to synthesize cyclohexanone oxime from nitrite (NO2-) and cyclohexanone under ambient conditions using a low-cost Cu-S catalyst, avoiding complex procedures, noble metal catalysts and H2SO4/H2O2 usage. This strategy produces 92% yield and 99% selectivity of cyclohexanone oxime, comparable to the industrial route. The reaction undergoes a NO2- → NH2OH→oxime reaction pathway. This electrocatalytic strategy is suitable for the production of other oximes, highlighting the methodology universality. The amplified electrolysis experiment and techno-economic analysis confirm its practical potential. This study opens a mild, economical, and sustainable way for the alternative production of cyclohexanone oxime.

Chronic exposure to (2 R,6 R)-hydroxynorketamine induces developmental neurotoxicity in hESC-derived cerebral organoids.

(R,S)-ketamine (ketamine) has been increasingly used recreationally and medicinally worldwide; however, it cannot be removed by conventional wastewater treatment plants. Both ketamine and its metabolite norketamine have been frequently detected to a significant degree in effluents, aquatic, and even atmospheric environments, which may pose risks to organisms and humans via drinking water and aerosols. Ketamine has been shown to affect the brain development of unborn babies, while it is still elusive whether (2 R,6 R)-hydroxynorketamine (HNK) induces similar neurotoxicity. Here, we investigated the neurotoxic effect of (2 R,6 R)-HNK exposure at the early stages of gestation by applying human cerebral organoids derived from human embryonic stem cells (hESCs). Short-term (2 R,6 R)-HNK exposure did not significantly affect the development of cerebral organoids, but chronic high-concentration (2 R,6 R)-HNK exposure at day 16 inhibited the expansion of organoids by suppressing the proliferation and augmentation of neural precursor cells (NPCs). Notably, the division mode of apical radial glia was unexpectedly switched from vertical to horizontal division planes following chronic (2 R,6 R)-HNK exposure in cerebral organoids. Chronic (2 R,6 R)-HNK exposure at day 44 mainly inhibited the differentiation but not the proliferation of NPCs. Overall, our findings indicate that (2 R,6 R)-HNK administration leads to the abnormal development of cortical organoids, which may be mediated by inhibiting HDAC2. Future clinical studies are needed to explore the neurotoxic effects of (2 R,6 R)-HNK on the early development of the human brain.

Antibacterial properties of antimicrobial peptide HHC36 modified polyetheretherketone.

Introduction: Polyetheretherketone (PEEK) is considered to be a new type of orthopedic implant material due to its mechanical properties and biocompatibility. It is becoming a replacement for titanium (Ti) due to its near-human-cortical transmission and modulus of elasticity. However, its clinical application is limited because of its biological inertia and susceptibility to bacterial infection during implantation. To solve this problem, there is an urgent need to improve the antibacterial properties of PEEK implants. Methods: In this work, we fixed antimicrobial peptide HHC36 on the 3D porous structure of sulfonated PEEK (SPEEK) by a simple solvent evaporation method (HSPEEK), and carried out characterization tests. We evaluated the antibacterial properties and cytocompatibility of the samples in vitro. In addition, we evaluated the anti-infection property and biocompatibility of the samples in vivo by establishing a rat subcutaneous infection model. Results: The characterization test results showed that HHC36 was successfully fixed on the surface of SPEEK and released slowly for 10 days. The results of antibacterial experiments in vitro showed that HSPEEK could reduce the survival rate of free bacteria, inhibit the growth of bacteria around the sample, and inhibit the formation of biofilm on the sample surface. The cytocompatibility test in vitro showed that the sample had no significant effect on the proliferation and viability of L929 cells and had no hemolytic activity on rabbit erythrocytes. In vivo experiments, HSPEEK can significantly reduce the bacterial survival rate on the sample surface and the inflammatory reaction in the soft tissue around the sample. Discussion: We successfully loaded HHC36 onto the surface of SPEEK through a simple solvent evaporation method. The sample has excellent antibacterial properties and good cell compatibility, which can significantly reduce the bacterial survival rate and inflammatory reaction in vivo. The above results indicated that we successfully improved the antibacterial property of PEEK by a simple modification strategy, making it a promising material for anti-infection orthopedic implants.

Influence of home chaos on preschool migrant children's resilience: A moderated mediation model.

Increasing attention has been drawn to the development of preschool migrant children's resilience recently. Resilience refers to the positive internal strengths and qualities of individuals in adverse situations, and is an essential psychological quality for preschool migrant children to cope with adversity. Home chaos as a risk factor, has an important impact on the development of individual's resilience, but the specific mechanisms under which home chaos works have yet to be explored, especially for preschool migrant children. Based on resilience model theory, 3,135 preschool migrant children and their families were surveyed and a moderated mediating effect mode was constructed to test the effect of home chaos on preschool migrant children's resilience. The results showed that after controlling for gender and age, home chaos significantly and negatively predicted preschool migrant children's resilience. Family resilience played a mediating role in the relationship between home chaos and preschool migrant children's resilience. Meanwhile, social support positively moderated the mediating effects of family resilience. The findings of this study suggested that low home chaos was conducive to promoting family resilience, which in turn fostered children's resilience, and that social support could play its protective role in weakening the negative effects of home chaos and this had certain guiding implications for the development of resilience in preschool migrant children.

Osseointegration behavior of carbon fiber reinforced polyetheretherketone composites modified with amino groups: An in vivo study.

Polyetheretherketone (PEEK) has become increasingly popular in dentistry and orthopedics due to its excellent chemical stability, reliable biosafety, and low elastic modulus. However, PEEK's biomechanical strength and bioactivity are limited and need to be increased as an implant material. The previous study in vitro has shown that the amino-functionalized carbon fiber reinforced PEEK (A-30%-CPEEK) possessed enhanced mechanical property and bioactivity. This study aims to evaluate the effect of amino groups modification on the osseointegration behavior of carbon fiber reinforced PEEK (30%-CPEEK) in rabbits. Herein, 30%-CPEEK and A-30%-CPEEK implant discs were implanted in rabbit skulls for 5 weeks, with pure titanium implants serving as a control. The bone-forming ability and osseointegration in vivo were systematically investigated by micro-computed tomography analysis, scanning electron microscope observation, and histological evaluation. Our results showed that all detection parameters were significantly different between the A-30%-CPEEK and 30%-CPEEK groups, favoring those in the A-30%-CPEEK, whose appraisal parameters were equal to or better than pure titanium. Therefore, this study supported the importance of amino groups in facilitating the new bone formation and bone-implant integration, suggesting that A-30%-CPEEK with enhanced osseointegration will be a promising material for dental or orthopedic implants.

Observation on the Efficacy of a Combined Treatment for Moderate and Severe Androgenetic Alopecia Incorporating Electric Microneedles.

Objective: To evaluate the effectiveness and safety of a combined treatment for moderate and severe androgenetic alopecia (AGA) involving the use of electric microneedles. Methods: A total of 83 patients with moderate to severe AGA in the Department of Dermatology at Beijing Jishuitan Hospital were included in this study. The male patients were administered finasteride orally and 5% minoxidil for external use, while the female patients were given spironolactone orally or Diane-35 and 2% minoxidil for external use. All the patients were then treated via electric microneedle therapy alongside the YUFA ®medical care package (Foshan, China) once a week for 1-28 weeks. The seven-point method and root hair measurement using a hair mirror were adopted to evaluate the efficacy and any adverse reactions of the combined treatment. Results: Eleven patients were treated for 1-3 weeks, 60 for 4-12 weeks, and 12 for more than 12 weeks. The efficacy evaluation using the seven-point method for 12 weeks of treatment indicated a 100% response rate, specifically, a 42.1% mild improvement rate, a 38.6% moderate improvement rate, and a 19.3% marked improvement rate. Besides, the efficacy assessment was also completed with root hair count method and the number of hair roots measured at fixed points were 148.67±11.15, 158.13±5.11 and 169.75±2.06 after treatment time at 16, 20 and 24 weeks, respectively. Of note, a statistical difference in the number of hair roots could be observed during the period of week 20-week 24 (P < 0.01). Conclusion: The combined treatment of moderate to severe AGA using the electric microneedle technique has a clear effect and can effectively increase the hair density. With a simple operation and mild side effects, the technique has wide application prospects.