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Neuronal radial migration is a fundamental process for cortical development, the disruption of which causes neurological and psychiatric dysfunctions. SLIT2 plays diverse functions in brain development and is a well-known axon guidance molecule. In this study, we investigated the radial migration of projection neurons in the developing cerebral cortex by in utero knockdown (KD) of Slit2 in mice. KD of Slit2 did not interfere with the neurogenesis and fate-determination but led to the accumulation of the transfected cells in the intermediate zone (IZ), suggesting that the expression of Slit2 is crucial for the radial migration of the cortical neurons. KD of Slit2 hindered the transition of cells from a multipolar to a bipolar shape, which is necessary for glia-guided locomotion. Interestingly, reducing Slit2 did not affect the migration of neighboring untransfected cells, indicating a cell-autonomous action by SLIT2. In addition, the action of SLIT2 KD was mimicked by a dominant negative mutant of ROBO2, a canonical membrane receptor of SLIT2, supporting that SLIT2 acted locally as a secretory molecule. Our results suggest that SLIT2 is indispensable for the radial migration of cortical neurons through an autocrine signaling mechanism.

Background Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. Methods We employed cortex-specific Foxp1 knockout ( Foxp1 -cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. Results Foxp1 -cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. Limitations It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. Conclusions Foxp1 -cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.

FOXP1 is a member of FOXP subfamily transcription factors. Mutations in FOXP1 gene have been found in various development-related cognitive disorders. However, little is known about the etiology of these symptoms, and specifically the function of FOXP1 in neuronal development. Here, we report that suppression of Foxp1 expression in mouse cerebral cortex led to a neuronal migration defect, which was rescued by overexpression of Foxp1. Mice with Foxp1 knockdown exhibited ectopic neurons in deep layers of the cortex postnatally. The neuronal differentiation of Foxp1-downregulated cells was normal. However, morphological analysis showed that the neurons with Foxp1 deficiency had an inhibited axonal growth in vitro and a weakened transition from multipolar to bipolar in vivo. Moreover, we found that the expression of Foxp1 modulated the dendritic maturation of neurons at a late postnatal date. Our results demonstrate critical roles of Foxp1 in the radial migration and morphogenesis of cortical neurons during development. This study may shed light on the complex relationship between neuronal development and the related cognitive disorders.

The contribution of Cutibacterium acnes (C. acnes) infection to intervertebral disc degeneration (IDD) and the antibiotic therapy has evoked several controversies in recent years. While some microbiology studies report bacterial disc infection within IDD patients, others attribute the positive results to contamination during prolonged cultures. In addition to the clinical controversy, little was known about the mechanism of C. acnes-caused Modic changes (MCs) if C. acnes was the pathogenic factor. This study aimed to investigate the inflammatory mechanism of MCs induced by different phylotypes of C. acnes in patients with IDD. Specimens from sixty patients undergoing microdiscectomy for disc herniation were included, C. acnes were identified by anaerobic culture, followed by biochemical and PCR-based methods. The identified species of C. acnes were respectively inoculated into the intervertebral discs of rabbits. MRI and histological change were observed. Additionally, we detected MMP expression in the rabbit model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Of the 60 cases, 18 (30%) specimens were positive for C. acnes, and we identified 4 of 6 defined phylogroups: IA, IB, II and III. The rabbits that received Type IB or II strains of C. acnes showed significantly decreased T1WI and higher T2WI at eighth weeks, while strain III C. acnes resulted in hypointense signals on both T1WI and T2WI. Histological examination results showed that all of the three types of C. acnes could cause disc degeneration and endplates rupture. Moreover, endplate degeneration induced by type IB or II strains of C. acnes is related with MMP13 expression. Meanwhile, strain III C. acnes might upregulated the level of MMP3. This study suggested that C. acnes is widespread in herniated disc tissues. Different types of C. acnes could induce different MCs by increasing MMP expression.

This study sets different nitrogen concentration gradients to explore the impact of nitrogen concentration on biomass and lipid accumulation of Chlamydomonas reinhardtii under different light intensities. The results showed that the conditions for the accumulation of lipid in the algae were 30μE-m -2 -s -1 light intensity and 100 mg . mL -1 nitrogen concentration with the lipid content of C. reinhardtii was 39.79% and chlorophyll content was 17.08 mg . mL -1 . This study provides an experimental basis for the regulation of lipid production of C. reinhardtii by using nitrogen-deficient culture and provides a foundation for further utilization of genetic engineering methods to regulate the lipid metabolism of C. reinhardtii.

FOXP1 is a member of FOXP subfamily transcription factors. Mutations in FOXP1 gene have been found in various development-related cognitive disorders. However, little is known about the etiology of these symptoms, and specifically the function of FOXP1 in neuronal development. Here, we report that suppression of Foxp1 expression in mouse cerebral cortex led to a neuronal migration defect, which was rescued by overexpression of Foxp1. Mice with Foxp1 knockdown exhibited ectopic neurons in deep layers of the cortex postnatally. The neuronal differentiation of Foxp1-downregulated cells was normal. However, morphological analysis showed that the neurons with Foxp1 deficiency had an inhibited axonal growth in vitro and a weakened transition from multipolar to bipolar in vivo. Moreover, we found that the expression of Foxp1 modulated the dendritic maturation of neurons at a late postnatal date. Our results demonstrate critical roles of Foxp1 in the radial migration and morphogenesis of cortical neurons during development. This study may shed light on the complex relationship between neuronal development and the related cognitive disorders.

Electron microscopy has been widely used in the structural analysis of proteins, pharmaceutical products, and various functional materials in the past decades. However, one fact is often overlooked that the crystal structure might be sensitive to external environments and response manners, which will bring uncertainty to the structure determination and structure-property correlation. Here, we report the atomic-level ab initio structure determinations of microcrystals by combining 3D electron diffraction (3D ED) and environmental transmission electron microscope (TEM). Environmental conditions, including cryo, heating, gas and liquid, have been successfully achieved using in situ holders to reveal the simuli-responsive structures of crystals. Remarkable structural changes have been directly resolved by 3D ED in one flexible metal-organic framework, MIL-53, owing to the response of framework to pressures, temperatures, guest molecules, etc. Materials’ structure of are often sensitive to external stimuli, which will bring uncertainty to the structure determination. Here authors present a 3D electron diffraction approach to study the stimuli responsive structures of crystals with atomic precision under various environmental conditions.

Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. Despite their importance, the interplay between these pathways remains poorly understood. Using genetic and metabolic analyses in Saccharomyces cerevisiae , we elucidate how cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. We find that deficiencies in the Kennedy pathway limit nucleotide salvage, prompting compensatory activation of de novo nucleotide synthesis and the pentose phosphate pathway. This metabolic shift enhances the production of antioxidants such as NADPH and glutathione. Moreover, we observe that the Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, indicating its role in antioxidative defense as an adaptive mechanism in aged cells. Our findings highlight the critical role of phospholipid synthesis pathway choice in the integrative regulation of nucleotide metabolism, redox balance and membrane properties for cellular defense. Zhu et al. found that cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. Phospholipid synthesis acts as an integrative defense mechanism to sense and combat oxidative stress.

Background Suicide among university students in China constitutes a critical public health challenge. Although numerous studies have examined risk factors, most have relied on cross-sectional designs. Evidence from longitudinal studies, particularly regarding protective factors, remains limited. This systematic review and meta-analysis synthesizes longitudinal evidence to identify risk and protective factors for suicidal ideation and suicide attempts among Chinese university students. Methods Six electronic databases (three English-language and three Chinese-language databases) were systematically searched for longitudinal studies published up to October 2024. Eligible studies investigated predictors of suicidal ideation or suicide attempts among Chinese university students. Random-effects meta-analyses were conducted to estimate pooled effect sizes, expressed as odds ratios (ORs). Meta-regression analyses were used to examine temporal moderators, and heterogeneity and publication bias were assessed. Results Twenty-two longitudinal studies comprising 953,651 participants were included. The strongest predictors of subsequent suicidal ideation were prior suicidal ideation, anxiety, and early morning awakening. Suicide attempts were most strongly associated with prior non-suicidal self-injury, insomnia symptoms, and academic pressure. Higher levels of social support were associated with a reduced risk of suicidal ideation, whereas other examined protective factors were not statistically significant. Meta-regression analyses indicated that the predictive strength of depressive symptoms for suicidal ideation attenuated with longer follow-up periods. Conclusions Sleep disturbances, academic pressure, and prior suicidal ideation may represent important targets for early identification among Chinese university students. The findings highlight the importance of addressing both psychological vulnerabilities and contextual stressors in suicide prevention efforts. Future longitudinal research should adopt standardized measurements to enhance comparability and inform culturally tailored population-level prevention strategies.

Copper corrosion under elevated temperature, humidity, and salinity environments has always been an important challenge in the engineering application. To enhance the corrosion protection of copper, an anodic oxidation induced coordination polymerization strategy was proposed, in which copper ions are released and in situ coordinated with 1,4-benzenedithiol (BDT) molecules to construct a bilayer passivation film, which consists of an outer Cu-BDT coordination polymer layer (~5.2 nm) and an intermediate cuprous sulfide layer (~ 1.8 nm) intrinsically grown on the underlying copper substrate. This passivation film markedly improves corrosion resistance, reducing the corrosion current density over three orders of magnitude in salinity environments. It also demonstrates chemical and thermal stability under acidic, alkaline, and high-temperature conditions. DFT calculations demonstrate that the passivation film increases the adsorption energy barriers of corrosive species, including O 2 (from − 2.07 eV to − 0.18 eV) and Cl − (from − 1.12 eV to 0.13 eV) on the copper surface. Furthermore, the strategy has been integrated into a roll-to-roll system, highlighting its potential for large-scale application. This work presents an effective and innovative strategy for enhancing the corrosion protection of copper through the construction of a nano-scale (~7 nm) bilayer passivation film. This study reports an electrochemical coordination polymerization strategy that forms a nanoscale bilayer protective film on copper, greatly improving corrosion resistance while enabling industrial-scale processing such as roll-to-roll manufacturing.