Factor analysis and evaluation of one-year test-retest reliability of the 33-item Childhood Trauma Questionnaire in Chinese adolescents.

The 33-item Childhood Trauma Questionnaire (CTQ-33) is a recently developed tool expanded from the 28-item Childhood Trauma Questionnaire (CTQ-28) to assess childhood trauma events, which showed good test-retest reliability over 2 weeks. However, little is known regarding the factor structure and long-term test-retest reliability of the CTQ-33. To fill such a gap, this study investigated the factorial validity of the CTQ-33 and test-retest reliability of the scale over a relatively long interval of 1 year. Data on demographics, the CTQ-33 scores, and mental health statuses such as depressive/anxiety symptoms were collected in Chinese adolescents (n = 188) twice across a one-year period. Results of the confirmatory factor analysis (CFA) revealed that the Chinese version of CTQ-33 has close factor validity when compared to the original CTQ-28 in college students. Furthermore, the total and most subscale scores of the CTQ-33 have fair to good test-retest reliability (intra-class correlation coefficients >0.6 for the total score, and > 0.4 for most subscales), except for the physical abuse subscale. Moreover, we replicated previous findings of significant positive relationships between levels of different childhood trauma subtypes using the CTQ-33. These findings provide initial evidence supporting that the CTQ-33 is overall reliable to assess childhood traumatic events in adolescents over relatively long intervals.

Quercetin 7-rhamnoside from Sorbaria sorbifolia exerts anti-hepatocellular carcinoma effect via DHRS13/apoptotic pathway.

BACKGROUND: Previous research demonstrated the effects of Sorbaria sorbifolia (SS) in combating hepatocellular carcinoma (HCC). Despite SS's proven efficacy in treating HCC, the precise bioactive constituents contributing to its therapeutic benefits, along with the mechanisms behind them, warrant further exploration. PURPOSE: The objective of our study was to illuminate the possible elements, targets, and modulatory pathways employed by specific bioactive components in SS for HCC treatment. STUDY DESIGN: Using UPLC-Q-TOF-MS to analyze and quantify the bioactive constituents in the SS sample. By literature review, we gathered potential chemical constituents of SS. We used network pharmacology approaches to identify HCC-related targets of SS components, with an emphasis on core targets. To examine the core targets' importance in HCC biological processes, bioinformatics methods were utilized. Finally, molecular docking, MD simulations, and CESTA were employed to screen SS active ingredients capable of stably binding with core targets. To verify the anti-HCC effectiveness of these active components, we conducted several cellular experiments, including CCK8, wound healing, transwell, cell cycle, and apoptosis assays, as well as animal experiments like zebrafish HepG2 cell xenotransplantation, apoptosis assays, and HE staining. We also used lentivirus transfection to modulate core protein expression in HepG2 cells, creating cell models. Further cellular tests were performed to evaluate the ability of SS active ingredients to exert anti-HCC effects by interacting with the core protein to induce apoptosis. Finally, Western Blot and ELISA experiments were carried out to track changes in core protein and apoptosis-related pathway proteins after SS active ingredient treatment RESULTS: Our study identified 50 components in SS and 119 HCC-related target genes, with DHRS13 emerging as a core target. Further bioinformatics analysis indicated that DHRS13 expression in HCC patients correlated with prognosis and apoptotic pathways. Molecular docking revealed 20 active SS constituents effectively binding to DHRS13, MD simulations and CESTA pinpointed Quercetin 7-rhamnoside (Q7R) as the most stable binder. In-vitro and in-vivo tests verified Q7R's anti-HCC properties. Lentivirus transfection results showed that knockdown DHRS13 led to reduced cell growth and increased apoptosis, while overexpression DHRS13 led to increase cell growth and decrease apoptosis. Remarkably, our experiments found that Q7R acts as an inhibitor of DHRS13 and can reverse the suppressed apoptosis and excessive HCC proliferation caused by DHRS13 overexpression. CONCLUSION: Elevated DHRS13 expression contributes to HCC progression. Q7R effectively downregulates DHRS13, encouraging apoptosis and impeding HCC growth. As a result, Q7R shows potential as a therapeutic agent for HCC treatment, targeting the apoptotic pathway through DHRS13 regulation.

HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma.

Upon infection with herpes simplex virus 1 (HSV-1), the virus deploys multiple strategies to evade the host's innate immune response. However, the mechanisms governing this phenomenon remain elusive. Here, we find that HSV-1 leads to a decrease in overall m6A levels by selectively reducing METTL14 protein during early infection in glioma cells. Specifically, the HSV-1-encoded immediate-early protein ICP0 interacts with METTL14 within ND10 bodies and serves as an E3 ubiquitin protein ligase, targeting and ubiquitinating METTL14 at the lysine 156 and 162 sites. Subsequently, METTL14 undergoes proteasomal degradation. Furthermore, METTL14 stabilizes ISG15 mRNA mediated by IGF2BP3 to promote antiviral effects. Notably, METTL14 suppression significantly enhances the anti-tumor effect of oncolytic HSV-1 (oHSV-1) in mice bearing glioma xenografts. Collectively, these findings establish that ICP0-guided m6A modification controls the antiviral immune response and suggest that targeting METTL14/ISG15 represents a potential strategy to enhance the oncolytic activity of oHSV-1 in glioma treatment.

Transformation and drive mechanism of nitrogen functional genes at estuaries in dry and wet seasons.

The nitrogen cycle plays a vital role in maintaining ecological health and biodiversity. In aquatic systems, nitrogen transformation genes significantly contribute to biological nitrogen cycling. Although the function of these genes is known to be influenced by environmental factors, there is limited research exploring the relationship between nitrogen transformation genes and environmental factors. Therefore, the correlations, between nitrogen transformation genes and environmental factors, were investigated at the estuaries of Chaohu lake (China) in different seasons. The results showed that the values of temperature, pH, organic compounds, nitrogen, and dissolved oxygen were higher in dry season, whereas the abundance of the genes was lower in dry season. In addition, the abundance of the anaerobic ammoxidation gene was much lower than the nitrification gene and denitrification gene. The results indicated that biological nitrification and denitrification were the primary mechanisms for nitrogen removal at estuaries in different seasons, and the reduction of nitric oxide may be a limiting step in the denitrification process. The Co-occurrence Network and Mantel test indicated that, during the dry season, the temperature was the primary driver of ammonification and nitrification functions, the NO3- and NO2- were the primary drivers of denitrification, and the total nitrogen (TN) and NH4+ were the main drivers of anaerobic ammonia oxidation. During the wet season, the dissolved oxygen was the primary driver of ammonification and nitrification functions, the chemical oxygen demand was the primary driver of denitrification, and the TN was the main driver of anaerobic ammonia oxidation. This study provides valuable insights into nitrogen cycling in surface water, contributing to a better understanding of this important process.

A connectome-based model of delusion in schizophrenia using functional connectivity under working memory task.

Delusion is an important feature of schizophrenia, which may stem from cognitive biases. Working memory (WM) is the core foundation of cognition, closely related to delusion. However, the knowledge of neural mechanisms underlying the relationship between WM and delusion in schizophrenia is poorly investigated. Two hundred and thirty patients with schizophrenia (dataset 1: n = 130; dataset 2: n = 100) were enrolled and scanned for an N-back WM task. We constructed the WM-related whole-brain functional connectome and conducted Connectome-based Predictive Modelling (CPM) to detect the delusion-related networks and built the correlation model in dataset 1. The correlation between identified networks and delusion severity was tested in a separate, heterogeneous sample of dataset 2 that mainly includes early-onset schizophrenia. The identified delusion-related network has a strong correlation with delusion severity measured by the NO.20 item of SAPS in dataset 1 (r = 0.433, p = 2.7 × 10-7, permutation-p = 0.035), and can be validated in the same dataset by using another delusion measurement, that is, the P1 item of PANSS (r = 0.362, p = 0.0005). It can be validated in another independent dataset 2 (NO.20 item of SAPS for r = 0.31, p = 0.0024, P1 item of PANSS for r = 0.27, p = 0.0074). The delusion-related network comprises the connections between the default mode network (DMN), cingulo-opercular network (CON), salience network (SN), subcortical, sensory-somatomotor network (SMN), and visual networks. We successfully established correlation models of individualized delusion based on the WM-related functional connectome and showed a strong correlation between delusion severity and connections within the DMN, CON, SMN, and subcortical network.

Genetic Testing for Global Developmental Delay in Early Childhood.

Importance: Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. Objectives: To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. Design, Setting, and Participants: This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. Main Outcomes and Measures: The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. Results: The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. Conclusions and Relevance: In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

Key factors affecting NH3-N in the Huaihe River Basin due to human activities.

Human activity factors have a significant impact on changes in ammonia nitrogen (NH3-N) content in rivers. Existing research mainly focuses on human activity factors as type factors, and lacks research on the key factors affecting river NH3-N among human activity factors. Therefore, this paper aims to study the key factors affecting human activities on NH3-N in the Huaihe River through various statistical analysis methods. The study found that changes in NH3-N content in the Huaihe River are mainly affected by land use patterns in the basin. There are two different ways in which land use affects NH3-N in rivers: direct effects and indirect effects. We also studied the main pathways through which changes in key factors in human activities affect NH3-N in the Huaihe River by constructing a structural equation model. The results showed that crop sowing area and afforestation area have a significant direct effect on NH3-N in the Huaihe River. In addition, crop sowing area and afforestation area can also affect river NH3-N by regulating the amount of nitrogen fertilizer and human excrement. This study is of great significance for understanding how human activities regulate NH3-N content in rivers.

PLIN5 Suppresses Lipotoxicity and Ferroptosis in Cardiomyocyte via Modulating PIR/NF-κB Axis.

Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL)-1ß/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.

Clinical study on the safety and feasibility of AiWalker-K for lower limbs exercise rehabilitation in children with cerebral palsy.

BACKGROUND: Robotic-assisted gait training (RAGT) devices are effective for children with cerebral palsy (CP). Many RAGT devices have been created and put into clinical rehabilitation treatment. Therefore, we aimed to investigate the safety and feasibility of a new RAGT for children with CP. METHODS: This study is a cross-over design with 23 subjects randomly divided into two groups. The occurrence of adverse events and changes in heart rate and blood pressure were recorded during each AiWalker-K training. Additionally, Gross Motor Function Measure-88 (GMFM-88), Pediatric Balance Scale (PBS), 6 Minutes Walking Test (6MWT), Physiological Cost Index, and Edinburgh Visual Gait Score (EVGS) were used to assess treatment, period, carry-over, and follow-up effects in this study. RESULTS: Adverse events included joint pain, skin pain, and injury. Heart rate and blood pressure were higher with the AiWalker-K compared to the rest (P < 0.05), but remained within safe ranges. After combined treatment with AiWalker-K and routine rehabilitation treatment, significant improvements in 6MWT, GMFM-88 D and E, PBS, and EVGS were observed compared to routine rehabilitation treatment alone (P < 0.05). CONCLUSIONS: Under the guidance of experienced medical personnel, AiWalker-K can be used for rehabilitation in children with CP.

The neural compensation phenomenon in schizophrenia with mild attention deficits during working memory task.

BACKGROUND: Working memory (WM) and attention are essential cognitive processes, and their interplay is critical for efficient information processing. Schizophrenia often exhibits deficits in both WM and attention, contributing to function impairments. This study aims to investigate the neural mechanisms underlying the relationship between WM impairments and attention deficits in schizophrenia. METHODS: We assessed the functional-MRI scans of the 184 schizophrenias with different attention deficits (mild=133; severe=51) and 146 controls during an N-back WM task. We explored their whole-brain functional connectome profile by adopting the voxel-wise degree centrality (DC). Linear analysis was conducted to explore the associations among attention deficit severity, altered DC, and WM performance in patients. RESULTS: We observed that all patients showed decreased DC in the pre-supplementary area (pre-SMA), and posterior cerebellum compared to the controls, and schizophrenia patients with mild attention deficits showed decreased DC in the supramarginal gyrus, insula, and precuneus compared with the other 2 groups. DC values of the detected brain regions displayed U-shaped or inverted U-shaped curves, rather than a linear pattern, in response to increasing attention deficits. The linear analysis indicated that altered DC of the pre-SMA can modulate the relationship between attention deficits and WM performance. CONCLUSION: The U-shaped or inverted U-shaped pattern in response to increasing attention deficits may reflect a compensation mechanism in schizophrenia with mild attention deficits. This notion is also supported by the linear analysis that schizophrenia patients with mild attention deficits can improve their WM performance by increasing the DC value of the pre-SMA.

Efficacy of a Soft Robotic Exoskeleton to Improve Lower Limb Motor Function in Children with Spastic Cerebral Palsy: A Single-Blinded Randomized Controlled Trial.

PURPOSE: Soft robotic exoskeletons (SREs) are portable, lightweight assistive technology with therapeutic potential for improving lower limb motor function in children with cerebral palsy. To understand the effects of long-term SRE-assisted walking training on children with spastic cerebral palsy (SCP), we designed a study aiming to elucidate the effects of SRE-assisted walking training on lower limb motor function in this population. METHODS: In this randomized, single-blinded (outcome assessor) controlled trial, forty children diagnosed with SCP were randomized into the routine rehabilitation (RR) group (N = 20) and the SRE group (N = 20) for comparison. The RR group received routine rehabilitation training, and the SRE group received routine rehabilitation training combined with SRE-assisted overground walking training. Assessments (without SRE) were conducted pre- and post-intervention (8 weeks after the intervention). The primary outcome measures included the 10 m walk test (10MWT) and the 6 min walk test (6MWT). Secondary outcome measures comprised the gross motor function measure-88, pediatric balance scale modified Ashworth scale, and physiological cost index. RESULTS: Both groups showed significant improvements (p < 0.01) across all outcome measures after the 8-week intervention. Between-group comparisons using ANCOVA revealed that the SRE group demonstrated greater improvement in walking speed from the 10MWT (+6.78 m/min, 95% CI [5.74-7.83]; p < 0.001) and walking distance during the 6MWT (+34.42 m, 95% CI [28.84-39.99]; p < 0.001). The SRE group showed greater improvement in all secondary outcome measures (p < 0.001). CONCLUSIONS: The study findings suggested that the integration of SRE-assisted overground walking training with routine rehabilitation more effectively enhances lower limb motor function in children with SCP compared to routine rehabilitation alone.

Source-specific probabilistic health risk assessment of heavy metals in surface water of the Yangtze River Basin.

The detrimental effects of heavy metal accumulation on both ecosystems and public health have raised widespread concern. Source-specific risk assessment is crucial for developing effective strategies to prevent and control heavy metal contamination in surface water. This study aims to investigate the contamination characteristics of heavy metals in the Yangtze River Basin, identifying the pollution sources, assessing the risk levels, and further evaluating the health risks to humans. The results indicated that the average concentrations of heavy metals were ranked as follows: zinc (Zn) > arsenic (As) > copper (Cu) > chromium (Cr) > cadmium (Cd) > nickel (Ni) > lead (Pb), with average concentrations of 38.02 µg/L, 4.34 µg/L, 2.53 µg/L, 2.10 µg/L, 1.17 µg/L, 0.84 µg/L, and 0.32 µg/L, respectively, all below the WHO 2017 standards for safe drinking water. The distribution trend indicates higher concentrations in the upper and lower reaches and lower concentrations in the mid-reaches of the river. By integrating the Absolute Principal Component Scores-Multiple Linear Regression (APCS-MLR) receptor model and Positive Matrix Factorization (PMF) model, the main sources of heavy metals were identified as industrial activities (APCS-MLR: 41.3 %; PMF: 42.1 %), agricultural activities (APCS-MLR: 30.1 %; PMF: 27.4 %), and unknown mix sources (APCS-MLR: 29.1 %; PMF: 30.4 %). The calculation of the hazard index (HI) for both children and adults was <1, indicating no non-carcinogenic or carcinogenic risks. Based on the source-specific risk assessment, agricultural activities contribute the most to non-carcinogenic risks, while industrial activities pose the greatest contribution to carcinogenic risks. This study offers a reference for monitoring heavy metals and controlling health risks to residents, and provides crucial evidence for the utilization and protection of surface water in the Yangtze River Basin.

The effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke: a meta-analysis.

BACKGROUND: Respiratory muscle training is a continuous and standardized training of respiratory muscles, but the evidence of the effects on early stroke patients is not clear. This meta-analysis aimed to investigate the effects of respiratory muscle training on respiratory function and functional capacity in patients with early stroke. METHODS: PubMed, Embase, PEDro, ScienceDirect, AMED, CINAHL, and China National Knowledge Infrastructure databases were searched from inception to December 8, 2023 for articles about studies that 1) stroke patients with age ≥ 18 years old. Early stroke < 3 months at the time of diagnosis, 2) respiratory muscle training, including inspiratory and expiratory muscle training, 3) the following measurements are the outcomes: respiratory muscle strength, respiratory muscle endurance, pulmonary function testing, dyspnea fatigue score, and functional capacity, 4) randomized controlled trials. Studies that met the inclusion criteria were extracted data and appraised the methodological quality and risk of bias using the Physiotherapy Evidence Database scale and the Cochrane Risk of Bias tool by two independent reviewers. RevMan 5.4 with a random effect model was used for data synthesis and analysis. Mean differences (MD) or standard mean differences (SMD), and 95% confidence interval were calculated (95%CI). RESULTS: Nine studies met inclusion criteria, recruiting 526 participants (mean age 61.6 years). Respiratory muscle training produced a statistically significant effect on improving maximal inspiratory pressure (MD = 10.93, 95%CI: 8.51-13.36), maximal expiratory pressure (MD = 9.01, 95%CI: 5.34-12.69), forced vital capacity (MD = 0.82, 95%CI: 0.54-1.10), peak expiratory flow (MD = 1.28, 95%CI: 0.94-1.63), forced expiratory volume in 1 s (MD = 1.36, 95%CI: 1.13-1.59), functional capacity (SMD = 0.51, 95%CI: 0.05-0.98) in patients with early stroke. Subgroup analysis showed that inspiratory muscle training combined with expiratory muscle training was beneficial to the recovery of maximal inspiratory pressure (MD = 9.78, 95%CI: 5.96-13.60), maximal expiratory pressure (MD = 11.62, 95%CI: 3.80-19.43), forced vital capacity (MD = 0.87, 95%CI: 0.47-1.27), peak expiratory flow (MD = 1.51, 95%CI: 1.22-1.80), forced expiratory volume in 1 s (MD = 0.76, 95%CI: 0.41-1.11), functional capacity (SMD = 0.61, 95%CI: 0.08-1.13), while inspiratory muscle training could improve maximal inspiratory pressure (MD = 11.60, 95%CI: 8.15-15.05), maximal expiratory pressure (MD = 7.06, 95%CI: 3.50-10.62), forced vital capacity (MD = 0.71, 95%CI: 0.21-1.21), peak expiratory flow (MD = 0.84, 95%CI: 0.37-1.31), forced expiratory volume in 1 s (MD = 0.40, 95%CI: 0.08-0.72). CONCLUSIONS: This study provides good-quality evidence that respiratory muscle training is effective in improving respiratory muscle strength, pulmonary function, and functional capacity for patients with early stroke. Inspiratory muscle training combined with expiratory muscle training seems to promote functional recovery in patients with early stroke more than inspiratory muscle training alone. TRIAL REGISTRATION: Prospero registration number: CRD42021291918.

Influence of TMX2-CTNND1 polymorphism on cortical thickness in schizophrenia patients and unaffected siblings: an exploratory study based on target region sequencing.

OBJECTIVE: The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. We aimed to estimate magnetic resonance imaging-derived cortical thickness across multiple brain regions. METHODS: The cortical thickness of 129 schizophrenia patients, 42 of their unaffected siblings, and 112 healthy controls was measured and the candidate genes were sequenced. Comparisons were made of cortical thickness (including 68 regions of the Desikan-Killiany Atlas) and genetic variants (in 108 risk genes for schizophrenia) among the three groups, and correlation analyses were performed regarding cortical thickness, clinical symptoms, cognitive tests (such as the N-back task and the logical memory test), and genetic variants. RESULTS: Schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyri than healthy controls and unaffected siblings. Association analyses in target genes showed that four single nucleotide variants (SNVs) were significantly associated with schizophrenia, including thioredoxin-related transmembrane protein 2-catenin, cadherin-associated protein, delta 1 (SNV20673) (positive false discovery rate [PFDR] = 0.008) and centromere protein M (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in the right pars triangularis was lower in carriers of the SNV20673 variant than in non-carriers (PFDR = 0.048). Finally, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). CONCLUSIONS: This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca's area, which was associated with a risk variant that affected delta-1 catenin and logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: circAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSIONS: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Tracing sulfate sources and transformations of surface water using multiple isotopes in a mining-rural-urban agglomeration area.

Rapid urbanization and mining activities are exacerbating sulfate (SO42-) pollution in surface water, and the information on its sources and transformations is crucial for understanding the sulphur cycle in mining areas. In this study, the SO42- in the surface water of Huaibei mining area were monitored and the main sources of pollution and biogeochemical processes were identified using stable isotopes (δD, δ18O-H2O, δ34S-SO42- and δ18O-SO42-) and water chemistry. The results demonstrated the SO42- content in the Huihe River and Linhuan subsidence water area (SWA) is higher than that in other rivers and SWAs, which exceeded the environmental quality standard of surface water. The SO42- content of different rivers and SWAs showed seasonal differences, and the dry season was higher than the wet season. In addition, the SO42- in Tuohe River and Suihe River is primarily caused by urban sewage and agriculture activities, while in Zhonghu and Shuoxihu SWA is mainly contributed by natural evaporate dissolution. Notably, the input of SO42- in the Huihe River and Linhuan SWA caused by mining activities cannot be disregarded. The aerobic environment and isotopic fractionation of surface water indicate that sulfide oxidation is not the major cause of SO42- formation. This work has revealed the multiple sources and transformation mechanisms of SO42-, and provided a reference for the development of comprehensive management and effective remediation strategies of SO42- contamination in surface water around mining areas.

Identification of nitrate accumulation mechanism of surface water in a mining-rural-urban agglomeration area based on multiple isotopic evidence.

The accumulation of nitrate (NO3-) in surface waters resulting from mining activities and rapid urbanization has raised widespread concerns. Therefore, it is crucial to develop a nitrate transformation information system to elucidate the nitrogen cycle and ensure sustainable water quality management. In this study, we focused on the main river and subsidence area of the Huaibei mining region to monitor the temporal and spatial variations in the NO3- content. Multiple isotopes (δD, δ18O-H2O, δ15N-NO3-, δ18O-NO3-, and δ15N-NH4+) along with water chemistry indicators were employed to identify the key mechanisms responsible for nitrate accumulation (e.g., nitrification and denitrification). The NO3- concentrations in surface water ranged from 0.28 to 7.50 mg/L, with NO3- being the predominant form of nitrogen pollution. Moreover, the average NO3- levels were higher during the dry season than during the wet season. Nitrification was identified as the primary process driving NO3- accumulation in rivers and subsidence areas, which was further supported by the linear relationship between δ15N-NO3- and δ15N-NH4+. The redox conditions and the relationship between δ15N-NO3- and δ18O-NO3-, and lower isotope enrichment factor of denitrification indicated that denitrification was weakened. Phytoplankton preferentially utilized available NH4+ sources while inhibiting NO3- assimilation because of their abundance. These findings provide direct evidence regarding the mechanism underlying nitrate accumulation in mining areas, while aiding in formulating improved measures for effectively managing water environments to prevent further deterioration.

Autosomal recessive intellectual disability caused by compound heterozygous variants of the EEF1D gene in a Chinese family.

BACKGROUND: Intellectual disability is a prevalent neurodevelopmental disorder, with the majority of affected children exhibiting global developmental delay before the age of 5 years. In recent years, certain children have been found to carry homozygous variations of the EEF1D gene, leading to autosomal recessive intellectual disability. However, the pathogenicity of compound heterozygous variations in this gene remains largely unknown. METHODS: Trio whole-exome sequencing and copy number variation sequencing were done for the genetic etiological diagnosis of a 3-year and 11-month-old Chinese boy who presented with brachycephaly, severe to profound global developmental delay, and hypotonia in the lower limbs. RESULTS: In this case, compound heterozygous variants of the EEF1D gene were found in the child through trio whole-exome sequencing; one was a splice variant (NM_032378.6:c.1905+1G>A) inherited from his father, and the other was a nonsense variant (NM_032378.6:c.676C>T) inherited from his mother. The nonsense variant leads to the production of a premature termination (p.Gln226*). These variations have the ability to explain the clinical phenotypes of the child. CONCLUSIONS: Our study expands the variation spectrum and provides compelling evidence for EEF1D as a candidate gene for autosomal recessive intellectual disability. However, due to the deficient number of reported cases, researchers need to further study EEF1D and supplement the clinical phenotypes and treatment measures.

Basin-wide tracking of nitrate cycling in Yangtze River through dual isotope and machine learning.

The nitrate (NO3-) input has adversely affected the water quality and ecological function in the whole basin of the Yangtze River. The protection of water sources and implementation of "great protection of Yangtze River" policy require large-scale information on water contamination. In this study, dual isotope and Bayesian mixing model were used to research the transformation and sources of nitrate. Chemical fertilizers contribute 76 % of the nitrate sources in the upstream, while chemical fertilizers were also dominant in the midstream (39 %) and downstream (39 %) of Yangtze River. In addition, nitrification process occurred in the whole basin. Four machine learning models were used to relate nitrate concentrations to explanatory variables describing influence factors to predict nitrate concentrations in the whole basin of Yangtze River. The anthropogenic and natural factors, such as rainfall, GDP and population were chosen to take as predictor variables. The eXtreme Gradient Boosting (XGBoost) model for nitrate has a better predictive performance with an R2 of 0.74. The predictive models of nitrate concentrations will help identify the nitrate distribution and transport in the whole Yangtze River basin. Overall, this study represents the first basin-wide data-driven assessment of the nitrate cycling in the Yangtze River basin.

Transparent silk fibroin film-facilitated infected-wound healing through antibacterial, improved fibroblast adhesion and immune modulation.

The clinical application of regenerated silk fibroin (RSF) films for wound treatment is restricted by its undesirable mechanical properties and lack of antibacterial activity. Herein, different pluronic polymers were introduced to optimize their mechanical properties and the RSF film with 2.5% pluronic F127 (RSFPF127) stood out to address the above issues owing to its satisfactory mechanical properties, hydrophilicity, and transmittance. Diverse antibacterial agents (curcumin, Ag nanoparticles, and antimicrobial peptide KR-12) were separately encapsulated in RSFPF127 to endow it with antibacterial activity. In vitro experiments revealed that the medicated RSFPF127 could persistently release drugs and had desirable bioactivities toward killing bacteria, promoting fibroblast adhesion, and modulating macrophage polarization. In vivo experiments revealed that medicated RSFPF127 not only eradicated methicillin-resistant Staphylococcus aureus in the wound area and inhibited inflammatory responses, but also facilitated angiogenesis and re-epithelialization, regardless of the types of antibacterial agents, thus accelerating the recovery of infected wounds. These results demonstrate that RSFPF127 is an ideal matrix platform to load different types of drugs for application as wound dressings.