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Many neuropsychiatric and neurodevelopmental disorders commonly share genetic risk factors. To date, the mechanisms driving the pathogenesis of these disorders, particularly how genetic variations affect the function of risk genes and contribute to disease symptoms, remain largely unknown. Neurexins are a family of synaptic adhesion molecules, which play important roles in the formation and establishment of synaptic structure, as well as maintenance of synaptic function. Accumulating genomic findings reveal that genetic variations within genes encoding neurexins are associated with a variety of psychiatric conditions such as schizophrenia, autism spectrum disorder, and some developmental abnormalities. In this review, we focus on NRXN1, one of the most compelling psychiatric risk genes of the neurexin family. We performed a comprehensive survey and analysis of current genetic and molecular data including both common and rare alleles within NRXN1 associated with psychiatric illnesses, thus providing insights into the genetic risk conferred by NRXN1. We also summarized the neurobiological evidences, supporting the function of NRXN1 and its protein products in synaptic formation, organization, transmission and plasticity, as well as disease-relevant behaviors, and assessed the mechanistic link between the mutations of NRXN1 and synaptic and behavioral pathology in neuropsychiatric disorders.

Objective The objective of the meta-analysis was to determine the influence of uterine fibroids on adverse outcomes, with specific emphasis on multiple or large (≥ 5 cm in diameter) fibroids. Materials and methods We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed databases for eligible studies that investigated the influence of uterine fibroids on adverse outcomes in pregnancy. The pooled risk ratio (RR) of the variables was estimated with fixed effect or random effect models. Results Twenty-four studies with 237 509 participants were included. The pooled results showed that fibroids elevated the risk of adverse outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, preterm premature rupture of membranes (PPROM), placental abruption, postpartum hemorrhage (PPH), fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjusting for the potential factors, negative effects were only seen for preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal death, breech presentation, and preeclampsia. Subgroup analysis showed an association between larger fibroids and significantly elevated risks of breech presentation, PPH, and placenta previa in comparison with small fibroids. Multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, and intrauterine growth restriction. Meta-regression analyses indicated that maternal age only affected the relationship between uterine fibroids and preterm birth, and BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH. Conclusion The presence of uterine fibroids poses increased risks of adverse pregnancy and obstetric outcomes. Fibroid size influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers had no impact on the risk of these outcomes.

Although the use of adaptive pulleys enhances the motion characteristics of cable-driven parallel robots (CDPRs), it significantly increases the complexity of the kinematics model. Conventional methods often fail to account for the influence of adaptive pulley motion on cable length variation, making it difficult to establish a precise kinematics model. To deal with the problem, this study presents a kinematic modeling and solution method for CDPRs, which incorporates adaptive pulley kinematics. First, the structural design of the CDPR driven by eight cables is analyzed. Then, the generalized kinematics model and the improved kinematics model with adaptive pulley considerations are established. Furthermore, a hybrid Levenberg–Marquardt and Genetic algorithm is proposed to achieve the efficient and high-precision solution of kinematics equations by combining the rapid global search and precise local optimization. Finally, the proposed method is validated through straight path simulation and elliptical path simulation. The simulation results indicate that the tracking accuracy of the end-effector is better than the 1 × 10−7 level for the proposed method.

Gaze direction can trigger social attentional orientation, characterised by a speeded reaction time in detecting targets appearing in a gazed-at location compared with those appearing in other locations. This is called the ‘gaze-cueing effect’ (GCE). Here, we investigated whether a feeling of guilt established through prior interaction with a cueing face could modulate the gaze-cueing effect. Participants first completed a guilt-induction task using a modified dot-estimation paradigm to associate the feeling of guilt with a specific face, after which the face that had established the binding relationship was used as the stimulus in a gaze-cueing task. The results showed that guilt-directed faces and control faces induce equal magnitudes of gaze-cueing effect in 200 ms of stimulus onset asynchrony (SOA), while guilt-directed faces induce a smaller gaze-cueing effect than control faces in 700 ms SOA. These findings provide preliminary evidence that guilt may modulate social attention triggered by eye gaze at a later stage of processing but not in the earlier stages.

BackgroundSepsis can cause brain damage known as septic encephalopathy (SAE), which is linked to higher mortality and poorer outcomes. Objective clinical markers for SAE diagnosis and prognosis are lacking. This study aimed to identify biomarkers of SAE by investigating genes and extracellular proteins involved in sepsis-induced brain injury.MethodsExtracellular protein differentially expressed genes (EP-DEGs) from sepsis patients’ brain tissue (GSE135838) were obtained from Gene Expression Omnibus (GEO) and evaluated by protein annotation database. The function and pathways of EP-DEGs were examined using GO and KEGG. Protein-protein interaction (PPI) networks were built and crucial EP-DEGs were screened using STRING, Cytoscape, MCODE, and Cytohubba. The diagnostic and prognostic accuracy of key EP-DEGs was assessed in 31 sepsis patients’ blood samples and a rat cecal ligation and puncture (CLP)-induced sepsis model. Cognitive and spatial memory impairment was evaluated 7-11 days post-CLP using behavioral tests. Blood and cerebrospinal fluid from 26 rats (SHAM n=14, CLP n=12) were collected 6 days after CLP to analyze key EP-DEGs.ResultsThirty-one EP-DEGs from DEGs were examined. Bone marrow leukocytes, neutrophil movement, leukocyte migration, and reactions to molecules with bacterial origin were all enhanced in EP-DEGs. In comparison to the sham-operated group, sepsis rats had higher levels of MMP8 and S100A8 proteins in their venous blood (both p <0.05) and cerebrospinal fluid ( p =0.0506, p <0.0001, respectively). Four important extracellular proteins, MMP8, CSF3, IL-6, and S100A8, were identified in clinical peripheral blood samples. MMP8 and S100A8 levels in the peripheral blood of sepsis patients were higher in SAE than in non-SAE. In comparison to MMP8, S100A8 had a higher area under the curve (AUC: 0.962, p <0.05) and a higher sensitivity and specificity (80% and 100%, respectively) than MMP8 (AUC: 0.790, p <0.05). High levels of S100A8 strongly correlated with 28-day mortality and the Glasgow Coma Scale (GCS) scores.ConclusionThe extracellular proteins MMP8, CSF3, IL-6, and S100A8 may be crucial in the pathophysiology of SAE. S100A8 and MMP8 are possible biomarkers for SAE’s onset and progression. This research may help to clarify the pathogenesis of SAE and improve the diagnosis and prognosis of the disease.

Recent studies have found that face masks affect social cognition and behaviour in the context of the novel coronavirus (COVID-19) pandemic. The eyes, the only part of the face not covered by face masks, are an important spatial attention cue that can trigger social attention orienting. Here, we adopted a spatial gaze-cueing task to investigate whether face masks affect social attention orienting triggered by eye gaze cues. In Experiment 1, participants were asked to determine the orientation of a target line under two types of cues—masked and non-masked faces—and two stimulus onset asynchrony (SOA) conditions (300 ms and 1000 ms). The results showed that masked faces induced a smaller gaze-cueing effect (GCE) compared to non-masked faces at 300 ms SOA, while two face types induced similar GCEs at 1000 ms SOA. Experiment 2 used mouth-obscured faces and non-masked faces as cues and found that no significant difference in GCE between the two types at either 300 ms or 1000 ms SOA, indicating that the reduction of GCE caused by the masked face was due to the social meaning expressed by the mask rather than a physical effect of masking. The present study extends previous findings to support the idea that high-level social information affects the processing of eye gaze direction and provides evidence that face masks affect social cognition and behaviour in the context of COVID-19.

Objective To assess the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII), as diagnostic markers for neonatal sepsis. Methods This retrospective study involve neonates with sepsis and healthy neonates as controls. NLR, PLR, and SII were compared between groups. Result In total, 60 neonates with sepsis and 60 healthy controls were involved in the study. Compared with controls, the sepsis group had higher values for NLR, PLR and SII. Logistic regression analysis suggested that the NLR, PLR and SII were independent risk factors for neonatal sepsis. In addition, receiver operating characteristic (ROC) curve analysis indicated that the NLR, PLR and SII were reliable predictors of neonatal sepsis and SII had the best predictive value. Conclusions NLR, PLR and SII appear to be useful indicators for predicting neonatal sepsis.

Alternative splicing of schizophrenia risk genes, such as DRD2, GRM3, and DISC1, has been extensively described. Nevertheless, the alternative splicing characteristics of the growing number of schizophrenia risk genes identified through genetic analyses remain relatively opaque. Recently, transcriptomic analyses in human brains based on short-read RNA-sequencing have discovered many “local splicing” events (e.g., exon skipping junctions) associated with genetic risk of schizophrenia, and further molecular characterizations have identified novel spliced isoforms, such as AS3MTd2d3 and ZNF804AE3E4. In addition, long-read sequencing analyses of schizophrenia risk genes (e.g., CACNA1C and NRXN1) have revealed multiple previously unannotated brain-abundant isoforms with therapeutic potentials, and functional analyses of KCNH2-3.1 and Ube3a1 have provided examples for investigating such spliced isoforms in vitro and in vivo. These findings suggest that alternative splicing may be an essential molecular mechanism underlying genetic risk of schizophrenia, however, the incomplete annotations of human brain transcriptomes might have limited our understanding of schizophrenia pathogenesis, and further efforts to elucidate these transcriptional characteristics are urgently needed to gain insights into the illness-correlated brain physiology and pathology as well as to translate genetic discoveries into novel therapeutic targets.

During the transposition of a target satellite, dynamic coupling between the target satellite, the manipulators, and the base frequently leads to disturbances in the base’s attitude. To deal with the issue, this paper proposed a pose stabilization method for the base of the post-capture combined system using the feedforward compensation PD control. Firstly, the mission sequence for repositioning a target satellite using a discrete-serpentine heterogeneous dual-arm space robot (DSHDASR) was analyzed. The dynamics model of the combined system, composed of the DSHDASR and a target satellite, was established based on the Newton–Euler recursive formulation. Then, the pose stabilization method integrating dynamic feedforward compensation and PD control was developed to stabilize the base of the combined system. Finally, the mission of target satellite transposition was simulated through the co-simulation model. Compared with the traditional control algorithms, the position accuracy and attitude accuracy for the proposed method showed an overall improvement. The results demonstrated that the proposed method significantly reduced base pose errors under high-load and disturbed conditions.

Background Autosomal dominant optic atrophy (ADOA), a leading common inherited optic neuropathy, arises from progressive retinal ganglion cell degeneration, often linked to OPA1 mutations. OPA1, a mitochondrial GTPase, regulates mitochondrial fusion, crista structure, and apoptosis. While GTPase-related dysfunction is well-studied, the role of other OPA1 domains in ADOA pathology remains unclear. Methods To investigate ADOA-linked OPA1 mutations, we assessed mitochondrial morphology, membrane potential, cytochrome c release, and cell viability in primary cortical neurons and N2a cells expressing OPA1 wild-type or mutant constructs. RNA sequencing and structural predictions (SWISS-MODEL) provided insights into molecular pathways and structural impacts. Results Two ADOA-associated mutations were characterized: V465F (GTPase β-fold) and V560F (BSE α-helix). Both mutations impaired mitochondrial fusion and cell survival under apoptotic stimuli. Notably, the BSE-located V560F mutation caused greater deficits in membrane potential maintenance, earlier apoptosis, and distinct molecular pathway changes compared to V465F. Conclusions This study highlights the domain-specific impacts of OPA1 mutations on mitochondrial function and ADOA pathology, revealing unique roles of the BSE domain in apoptosis regulation and mitochondrial integrity. These findings provide insights into ADOA mechanisms and potential therapeutic targets.