A longitudinal study on the development trajectory of auditory processing and its relationship with language development in Chinese preschool children with autism spectrum disorder: study protocol.

BACKGROUND: It was reported that more than 96% of autism spectrum disorder (ASD) children are accompanied with different degrees of sensory processing abnormalities, and up to 50% of ASD children exhibit abnormal auditory response. Studies have confirmed that some ASD children's abnormal auditory response may be related to their abnormal auditory processing. Prior research demonstrated that ASD children's auditory processing has high heterogeneity, thus, ASD children's auditory processing may have different developmental trajectories. However, no study has concentrated on the developmental trajectories of ASD children's auditory processing. In addition, auditory processing plays a crucial role in ASD children's language development, thus, ASD children's different language development outcomes may be related to different auditory processing development tracks. Therefore, this study aims to explore the developmental trajectory of auditory processing in ASD children and analyze the relationship between different developmental trajectories of auditory processing and language impairment. METHODS/DESIGN: In this study, 220 ASD children aging 3 years and 0 months to 4 years and 11 months are recruited as the research objects, and their demographic characteristics are collected. The subjects are tested for peripheral hearing, intelligence, and autism symptoms. Furthermore, ASD children's auditory processing and language development are evaluated at baseline, 1 year, and 2 years later. In addition, ASD children's auditory processing is evaluated by electrophysiological test and the Preschool Auditory Processing Assessment Scale. Moreover, ASD children's language skills are assessed using the Language Development Assessment Scale for Children Aged 1-6. The various categories of the developmental trajectory of ASD children's auditory processing are examined through the latent category growth model. Additionally, a hierarchical regression model is developed to analyze the predictive impact of different auditory processing development trajectories on language impairment in ASD children. DISCUSSION: This longitudinal study will explore the categories of auditory processing developmental trajectories in ASD children, and analyze the relationship between different categories of auditory processing developmental trajectories and language development, providing new ideas and targeted targets for the rehabilitation training of language impairment in ASD children, as well as promoting early and accurate interventions for ASD children.

Association between neural prosody discrimination and language abilities in toddlers: a functional near-infrared spectroscopy study.

BACKGROUND: Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. METHODS: In this study, all cases(n = 241) were enrolled from a tertiary women's hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children's neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. RESULTS: Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687. CONCLUSIONS: Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.

Protocol to fabricate a self-adhesive and long-term stable hydrogel for sleep EEG recording.

Long-term continuous electroencephalogram (EEG) monitoring is crucial for neuroengineering but suffers from hardware limitations. Here, we present a protocol for EEG recording using a long-term stable and reagent-free-cross-linked hydrogel with configurable mechanical and adhesive properties. We describe steps for fabricating the hydrogel and performing material characterizations and stability tests. We detail procedures for setting up the EEG recording configuration and data analysis. This protocol can facilitate EEG recording experiments with the hydrogel, as well as other novel materials and devices. For complete details on the use and execution of this protocol, please refer to Hsieh et al.1.

Mechanical-Enhanced and Durable Zwitterionic Hydrogel Coating for Inhibiting Coagulation and Reducing Bacterial Infection.

Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

Improving Accuracy of ADHD Diagnosis with the Combination of Brain Imaging and Behavioral Measures.

Neuropsychological measures may improve Attention-deficit/hyperactivity disorder (ADHD) diagnostic accuracy and enhance treatment response detection. Highquality evaluation indicators are necessary for accurate diagnosis of ADHD. Due to the high complexity of the pathogenesis of ADHD, it may not be possible to accurately diagnose ADHD only by relying on behavioral assessment or brain imaging examination. Therefore, the authors propose a comprehensive index that combines brain imaging behavioral and measures. The results showed that the classification performance of the composite index was better than that of the single behavior or brain image index.Clinical Relevance- The results of this study help to remind practicing clinicians to consider the results of multiple clinical examinations when clinically diagnosing ADHD patients.

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OBJECTIVES: To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them. METHODS: A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method. RESULTS: The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (ß=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect. CONCLUSIONS: The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

Injectable spontaneously formed asymmetric adhesive hydrogel with controllable removal for wound healing.

Healing large-scale wounds has been a long-standing challenge in the field of biomedicine. Herein, we propose an injectable oxidated sodium alginate/gelatin/3,3'-dithiobis(propionic hydrazide)-aurum (Alg-CHO/gelatin/DTPH-Au) hydrogel filler with asymmetric adhesion ability and removability, which is formed by the Schiff-base reaction between aldehyde-based sodium alginate and multi-amino crosslinkers (gelatin and DTPH), combined with the coordination interaction between Au nanoparticles and disulfide bond of DTPH. Consequently, the prepared Alg-CHO/gelatin/DTPH-Au hydrogel exhibits high mechanical properties and injectable behaviors owing to its multiple-crosslinked interactions. Moreover, because various types of interaction bonding form on the contact side with the tissue, denser crosslinking of the upper layer relative to the lower layer occurs. Combined with the temperature difference between the upper and lower surfaces, this results in asymmetric adhesive properties. Owing to the photothermal effect, the reversible coordination interaction between Au nanoparticles and DTPH and the change in the triple helix structure of gelatin to a coil structure impart the filler-phased removability and antibacterial ability. The choice of all natural polymers also allows for favorable degradability of the wound filler and outstanding biocompatibility. Based on these features, this versatile wound filler can achieve a wide range of applications in the field of all-skin wound repair.

Study on the factors of hydrogen sulfide production from lignite bacterial sulfate reduction based on response surface method.

Bacterial sulfate reduction (BSR) is one of the key factors leading to the anomalous accumulation of hydrogen sulphide in coal mines. Environmental factors such as temperature and pH play a crucial role in the metabolism and degradation of coal by sulfate-reducing bacteria (SRB). In this study, coal samples were selected from Shengli Coal Mine, and SRB strains were isolated and purified from mine water using a dilution spread-plate anaerobic cultivation method. Based on single-factor experiments and response surface methodology (RSM), the impact of temperature, pH, oxidation-reduction potential (ORP), chemical oxygen demand to sulfate ratio (COD/SO42-) on the generation of hydrogen sulphide during brown coal BSR was analyzed. The results showed that the anaerobic degradation of coal by SRB was inhibited by either too high or too low a temperature to produce hydrogen sulfide, and the greatest production of hydrogen sulfide occurred at a temperature of about 30 °C; The greatest production of hydrogen sulfide occurred at an initial ambient pH of 7.5; COD/SO42- ratio of around 2.0 is most conducive to hydrogen sulphide generation; the lower ORP value is more favorable for hydrogen sulfide generation. The optimal conditions obtained by RSM were: temperature of 30.37 °C, pH of 7.64 and COD/SO42- of 1.96. Under these conditions, the hydrogen sulfide concentration was 56.79 mg/L, the pH value was 8.40, the ORP value was -274 mV, and the SO42- utilization rate was 58.04%. The RSM results showed that temperature, ambient pH and COD/SO42- had a significant effect on hydrogen sulfide production, and the degree of effect was: ambient pH > temperature > COD/SO42-.

Chronological adhesive cardiac patch for synchronous mechanophysiological monitoring and electrocoupling therapy.

With advances in tissue engineering and bioelectronics, flexible electronic hydrogels that allow conformal tissue integration, online precision diagnosis, and simultaneous tissue regeneration are expected to be the next-generation platform for the treatment of myocardial infarction. Here, we report a functionalized polyaniline-based chronological adhesive hydrogel patch (CAHP) that achieves spatiotemporally selective and conformal embedded integration with a moist and dynamic epicardium surface. Significantly, CAHP has high adhesion toughness, rapid self-healing ability, and enhanced electrochemical performance, facilitating sensitive sensing of cardiac mechanophysiology-mediated microdeformations and simultaneous improvement of myocardial fibrosis-induced electrophysiology. As a result, the flexible CAHP platform monitors diastolic-systolic amplitude and rhythm in the infarcted myocardium online while effectively inhibiting ventricular remodeling, promoting vascular regeneration, and improving electrophysiological function through electrocoupling therapy. Therefore, this diagnostic and therapeutic integration provides a promising monitorable treatment protocol for cardiac disease.

Research progress of the Fanconi anemia pathway and premature ovarian insufficiency†.

The Fanconi anemia pathway is a key pathway involved in the repair of deoxyribonucleic acidinterstrand crosslinking damage, which chiefly includes the following four modules: lesion recognition, Fanconi anemia core complex recruitment, FANCD2-FANCI complex monoubiquitination, and downstream events (nucleolytic incision, translesion synthesis, and homologous recombination). Mutations or deletions of multiple Fanconi anemia genes in this pathway can damage the interstrand crosslinking repair pathway and disrupt primordial germ cell development and oocyte meiosis, thereby leading to abnormal follicular development. Premature ovarian insufficiency is a gynecological clinical syndrome characterized by amenorrhea and decreased fertility due to decreased oocyte pool, accelerated follicle atresia, and loss of ovarian function in women <40 years old. Furthermore, in recent years, several studies have detected mutations in the Fanconi anemia gene in patients with premature ovarian insufficiency. In addition, some patients with Fanconi anemia exhibit symptoms of premature ovarian insufficiency and infertility. The Fanconi anemia pathway and premature ovarian insufficiency are closely associated.

Strongly adhesive zwitterionic composite hydrogel paints for surgical sutures and blood-contacting devices.

Hydrogels show eminent advantages in biomedical and pharmaceutical fields. However, their application as coating materials for biomedical devices is limited by several key challenges, such as lack of universality, weak mechanical strength, and low adhesion to the substrate. Here we report versatile and tough adhesion composite hydrogel paints (CHPs), which consist of zwitterionic copolymers and microgels, both with reactive groups. The CHPs exhibit tunable rheology and thickness, hydrophilicity, biofouling resistance, durability, and convenient fabrication on metal, polymer, and inorganic surfaces with arbitrary shapes. As a proof-of-concept, the CHP-surgical sutures demonstrate exceptional lubrication, drug delivery, anti-infection, and anti-fibrous capsule properties. Moreover, the CHP-PVC tubing effectively prevents thrombus formation in vitro and ex vivo rabbit blood circulation without anticoagulants. This work provides valuable insights for enhancing and developing integrated hydrogel technologies for biomedical devices. STATEMENT OF SIGNIFICANCE: The combination of hydrogel and biomedical devices can enable numerous existing applications in medicine. In this study, inspired by the principle of microgel reinforcement in industrial paints, we propose a simple and versatile zwitterionic composite hydrogel paints (CHPs) strategy, which can be easily applied to diverse substrates with arbitrary shapes by covalent grafting between complementary groups by brush, dip, or spray. The CHPs integrated universality, tough adhesion, mechanical durability, and anti-biofouling properties because of their unique chemical composition and coating structure design. This strategy provides a simple and versatile route for surface modification of biomedical devices.

A self-gelling powder based on polyacrylic acid/polyacrylamide/quaternate chitosan for rapid hemostasis.

In order to improve the hemostatic effect of the hemostatic dressing for non-compressible wounds, unknown bleeding points and irregularly shaped wounds, a self-gelling hemostasis powder based on polyacrylic acid/polyacrylamide/quaternate chitosan (PAA/PAM/QCS) is prepared in this study. When in contact with water, the PAA/PAM/QCS can fuse and rapidly form a stable hydrogel in a short time (< 0.25 min). The PAA/PAM ratio is the main parameter that modulates the formation of the self-gel. The PAA/PAM self-gel can be formed only when the PAA/PAM ratio is 5:5, and the introduction of QCS does not influence the self-gelling behaviors and hydrogel stability. Moreover, the PAA/PAM/QCS self-gel shows good adhesive properties on wet tissue surfaces. In addition, the introduction of QCS improves the antibacterial activity of the self-gelling hemostasis powder. Furthermore, the prepared PAA/PAM/QCS powder can rapidly adsorb lots of blood, aggregate blood cells and platelets. The hemostatic results in vivo show that PAA/PAM/QCS powder is superior to the control group and commercial product groups (chitosan powder) with performance similar to hemostatic zeolite in terms of the amount of bleeding and hemostatic time. Therefore, the PAA/PAM/QCS self-gelling powder shows great application prospects for rapid hemostasis.

Zwitterionic Polysaccharide-Based Hydrogel Dressing as a Stem Cell Carrier to Accelerate Burn Wound Healing.

Stem cell therapy integrated with hydrogels has shown promising potential in wound healing. However, the existing hydrogels usually cannot reach the desired therapeutic efficacy for burn wounds due to the inadaptability to wound shape and weak anti-infection ability. Moreover, it is difficult to improve the environment for the survival and function of stem cells under complicated wound microenvironments. In this study, an injectable and self-healing hydrogel (DSC), comprising sulfobetaine-derived dextran and carboxymethyl chitosan, is fabricated through a Schiff-base reaction. Meanwhile, the DSC hydrogel shows high nonfouling properties, including resistance to bacteria and nonspecific proteins; moreover, the prepared hydrogel can provide a biomimetic microenvironment for cell proliferation whilst maintaining the stemness of adipose-derived stem cells (ADSCs) regardless of complex microenvironments. In burnt murine animal models, the ADSCs-laden hydrogel can significantly accelerate wound healing rate and scarless skin tissue regeneration through multiple pathways. Specifically, the ADSCs-laden DSC hydrogel can avoid immune system recognition and activation and thus reduce the inflammatory response. Moreover, the ADSCs-laden DSC hydrogel can promote collagen deposition, angiogenesis, and enhance macrophage M2 polarization in the wound area. In summary, sulfobetaine-derived polysaccharide hydrogel can serve as a versatile platform for stem cell delivery to promote burn wound healing.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.

Microgel reinforced zwitterionic hydrogel coating for blood-contacting biomedical devices.

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.