Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior.

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Transforming Red Phosphorus Photocatalysis: Dual Roles of Pre-Anchored Ru Single Atoms in Defect and Interface Engineering.

Crystalline red phosphorus(CRP), known for its promising photocatalytic properties, faces challenges in photocatalytic hydrogen evolution(PHE) due to undesired inherent charge deep trapping and recombination effects induced by defects. This study overcomes these limitations through an innovative strategy in integrating ruthenium single atoms(Ru1) within CRP to simultaneously repair the intrinsic undesired vacancy defects and serve as the uniformly distributed anchoring sites for a controllable growth into ruthenium nanoparticles(RuNP). Hence, a highly functionalized CRP with Ru1 and RuNP(Ru1-NP/CRP) with concerted effects in regulating electronic structures and promoting interfacial charge transfer has been achieved. Advanced characterizations unveil the pioneering dual role of pre-anchored Ru1 in transforming CRP photocatalysis. The regulations of vacancy defects on the surface of CRP minimize the detrimental deep charge trapping, resulting in the prolonged lifetime of charges. With the well-distributed in-situ growth of RuNP on Ru1 sites, the constructed robust "bridge" that connects CRP and RuNP facilitates constructive interfacial charge transfer. Ultimately, the synergistic effect induced by the pre-anchored Ru1 endows Ru1-NP/CRP with an exceptional PHE rate of 3175µmolh-1g-1, positioning it as one of the most efficient elemental-based photocatalysts. This breakthrough underscores the crucial role of pre-anchoring metal single atoms at defect sites of catalysts in enhancing hydrogen production.

Distribution and dynamic changes of Huanglongbing pathogen in its insect vector Diaphorina citri.

The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama is the leading vector of Candidatus Liberibacter asiaticus (CLas), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of CLas within ACP are critical to understanding how the transmission, spread and infection of CLas occurs within its host vector in nature. In this study, the distribution and titer changes of CLas in various tissues of ACP 5th instar nymphs and adults were examined by fluorescence in situ hybridization (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5th instar nymphs and adults were infected with CLas following feeding on infected plants, and that CLas had widespread distribution in most of the tissues of ACP. The titers of CLas within the midgut, salivary glands and hemolymph tissues were the highest in both 5th instar nymphs and adults. When compared with adults, the titers of CLas in these three tissues of 5th instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of CLas demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of CLas with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of CLas, which is of much importance for developing novel strategies to halt the spread of CLas, and therefore contribute to the efficient prevention and control of HLB.

A review of hierarchical porous carbon derived from various 3D printing techniques.

Hierarchical porous carbon is an area of advanced materials that plays a pivotal role in meeting the increasing demands across various industry sectors including catalysis, adsorption, and energy storage and conversion. Additive manufacturing is a promising technique to synthesize architectured porous carbon with exceptional design flexibility, guided by computer-aided precision. This review paper aims to provide an overview of porous carbon derived from various additive manufacturing techniques, including material extrusion, vat polymerization, and powder bed fusion. The respective advantages and limitations of these techniques will be examined. Some exemplary work on various applications will be showcased. Furthermore, perspectives on future research directions, opportunities, and challenges of additive manufacturing for porous carbon will also be offered.

Transcranial magnetic stimulation in the assessment of acupuncture effect on exercise-induced fatigue.

BACKGROUND: Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS). METHODS: A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise-induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5 min over a 30-min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0 min, and 30 min after fatigue. Two-way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p < .05. RESULTS: Interaction effect was observed between acupuncture method and time effect in terms of amplitude (F(1, 38) = 5.40, p < .001, η2 = 0.12) and latency (F(1, 38) = 3.78, p = .008, η2 = .09) of MEP. The application of acupuncture can promote the recovery of heart rate especially at 30 min (p < .05), but which seem insufficient to generate significant difference in BLA (F(1, 38) = 0.067, p = .797, η2 = 0.002). CONCLUSIONS: Acupuncture can promote the increase of MEP amplitude, shorten MEP latency, and restore heart rate. Preliminary findings provide novel insights for individuals with exercise habits to alleviate fatigue and enhance sports performance.

Establishment of droplet digital PCR for the detection of Neisseria gonorrhoeae.

BACKGROUND: Infection with Neisseria gonorrhoeae in adults usually leads to vaginitis and acute urethritis, and infection through the birth canal in newborns can lead to acute neonatal conjunctivitis. In view of certain factors such as a high missed detection rate of N.gonorrhoeae from staining microscopy method, the time-consuming nature and limited sensitivity of bacterial culture method, complicated and inability of absolute quantification from the ordinary PCR method. METHODS: This study aims to establish a ddPCR system to detect N.gonorrhoeae in a absolute quantification, high specificity, high stability and accurate way. We selected the pgi1 gene as the target gene for the detection of N.gonorrhoeae. RESULTS: The amplification efficiency was good in the ddPCR reaction, and the whole detection process could be completed in 94 min. It has a high sensitivity of up to 5.8 pg/µL. With a high specificity, no positive microdroplets were detected in 9 negative control pathogens in this experiment. In addition, ddPCR detection of N.gonorrhoeae has good repeatability, and the calculated CV is 4.2 %. CONCLUSIONS: DdPCR detection technology has the characteristics of absolute quantification, high stability, high specificity and high accuracy of N.gonorrhoeae. It can promote the accuracy of the detecting of N.gonorrhoeae, providing a more scientific basis for clinical diagnosis and treatment.

ABCD2-I Score Predicts Unplanned Emergency Department Revisits within 72 Hours Due to Recurrent Acute Ischemic Stroke.

BACKGROUND: the ABCD2 score is valuable for predicting early stroke recurrence after a transient ischemic attack (TIA), and Doppler ultrasound can aid in expediting stroke triage. The study aimed to investigate whether combining the ABCD2 score with carotid duplex results can enhance the identification of early acute ischemic stroke after TIA. METHODS: we employed a retrospective cohort design for this study, enrolling patients diagnosed with TIA who were discharged from the emergency department (ED). The modified ABCD2-I (c50) score, which incorporates a Doppler ultrasound assessment of internal carotid artery stenosis > 50%, was used to evaluate the risk of acute ischemic stroke within 72 h. Patients were categorized into three risk groups: low risk (with ABCD2 and ABCD2-I scores = 0-4), moderate risk (ABCD2 score = 4-5 and ABCD2-I score = 5-7), and high risk (ABCD2 score = 6-7 and ABCD2-I score = 8-9). RESULTS: between 1 January 2014, and 31 December 2019, 1124 patients with new neurological deficits were screened, with 151 TIA patients discharged from the ED and included in the analysis. Cox proportional hazards analysis showed that patients in the high-risk group, as per the ABCD2-I (c50) score, were significantly associated with revisiting the ED within 72 h due to acute ischemic stroke (HR: 3.12, 95% CI: 1.31-7.41, p = 0.0102), while the ABCD2 alone did not show significant association (HR: 1.12, 95% CI: 0.57-2.22, p = 0.7427). CONCLUSION: ABCD2-I (c50) scores effectively predict early acute ischemic stroke presentations to the ED within 72 h after TIA.

NanoMUD: Profiling of pseudouridine and N1-methylpseudouridine using Oxford Nanopore direct RNA sequencing.

Nanopore direct RNA sequencing provided a promising solution for unraveling the landscapes of modifications on single RNA molecules. Here, we proposed NanoMUD, a computational framework for predicting the RNA pseudouridine modification (Ψ) and its methylated analog N1-methylpseudouridine (m1Ψ), which have critical application in mRNA vaccination, at single-base and single-molecule resolution from direct RNA sequencing data. Electric signal features were fed into a bidirectional LSTM neural network to achieve improved accuracy and predictive capabilities. Motif-specific models (NNUNN, N = A, C, U or G) were trained based on features extracted from designed dataset and achieved superior performance on molecule-level modification prediction (Ψ models: min AUC = 0.86, max AUC = 0.99; m1Ψ models: min AUC = 0.87, max AUC = 0.99). We then aggregated read-level predictions for site stoichiometry estimation. Given the observed sequence-dependent bias in model performance, we trained regression models based on the distribution of modification probabilities for sites with known stoichiometry. The distribution-based site stoichiometry estimation method allows unbiased comparison between different contexts. To demonstrate the feasibility of our work, three case studies on both in vitro and in vivo transcribed RNAs were presented. NanoMUD will make a powerful tool to facilitate the research on modified therapeutic IVT RNAs and provides useful insight to the landscape and stoichiometry of pseudouridine and N1-pseudouridine on in vivo transcribed RNA species.

Real-world efficacy, roll-out and uptake of intramuscular tixagevimab/cilgavimab as COVID-19 pre-exposure prophylaxis in people with multiple sclerosis and neuroimmunological conditions during the COVID-19 pandemic.

Background: In Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible. Objective: To analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery. Methods: We undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented. Results: Of the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04). Conclusion: Tixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location.

Schottky Junction Enhanced Photosynthesis of Hydrogen Peroxide by Ultrathin Porous Carbon Nitride Supported Ni Nanoparticles.

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

Ulcerated nodules with zosteriform distribution on the upper extremity.

Eccrine porocarcinoma (EPC) is a rare skin adnexal malignancy with a high potential for metastases. The most common metastatic sites are the lymph nodes and lungs. CCutaneous metastasis is extremely rare, particularly the zosteriform variant, with fewer than 5 cases reported in the literature. Here, we report a unique case of EPC in a 71-year-old male, clinically presenting with multiple clusters of ulcerated nodules distributing as a zosteriform pattern throughout his upper left limb, along with draining lymphatic metastases and lymphedema.

m6ACali: machine learning-powered calibration for accurate m6A detection in MeRIP-Seq.

We present m6ACali, a novel machine-learning framework aimed at enhancing the accuracy of N6-methyladenosine (m6A) epitranscriptome profiling by reducing the impact of non-specific antibody enrichment in MeRIP-Seq. The calibration model serves as a genomic feature-based classifier that refines the identification of m6A sites, distinguishing those genuinely present from those that can be detected in in-vitro transcribed (IVT) control experiments. We find that m6ACali effectively identifies non-specific binding peaks reported by exomePeak2 and MACS2 in novel MeRIP-Seq datasets without the need for paired IVT controls. The model interpretation revealed that off-target antibody binding sites commonly occur at short exons and short mRNAs, originating from high read coverage regions that share the motif sequence with true m6A sites. We also reveal that the ML strategy can efficiently adjust differentially methylated peaks and other antibody-dependent, base-resolution m6A detection techniques. As a result, m6ACali offers a promising method for the universal enhancement of m6A profiles generated by MeRIP-Seq experiments, elevating the benchmark for omics-level m6A data integration.

Dysregulation of TCONS_00006091 contributes to the elevated risk of oral squamous cell carcinoma by upregulating SNAI1, IRS and HMGA2.

In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.

The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy.

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.

Dynamic changes in lysosome-related pathways in APP/PS1 mice with aging.

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Disrupted cognitive and affective empathy network interactions in autistic children viewing social animation.

Empathy can be divided into two core components, cognitive empathy (CE) and affective empathy (AE), mediated by distinct neural networks. Deficient empathy is a central feature of autism spectrum conditions (ASCs), but it is unclear if this deficit results from disruption solely within empathy networks or from disrupted functional integration between CE and AE networks. To address this issue, we measured functional connectivity (FC) patterns both within and between empathy networks in autistic children (4-8 years, n = 31) and matched typically developing (TD) children (n = 26) using near-infrared spectroscopy during the presentation of an animated story evoking CE and AE. Empathy and social communication ability were also assessed using the Empathy Quotient/Systemizing Quotient (EQ/SQ) and Social Responsiveness Scale, respectively. The results showed that the FC in the AE network of autistic children did not differ from the TD group across conditions; however, the ASC group showed weaker FC in the CE network under the CE condition and weaker FC between networks when processing AE information, the latter of which was negatively correlated with EQ scores in ASC. The empathy defect in ASC may involve abnormal integration of CE and AE network activities under AE conditions.

Prediction of vascular complications in free flap reconstruction with machine learning.

OBJECTIVE: This study aims to explore the risk factors of vascular complications following free flap reconstruction and to develop a clinical auxiliary assessment tool for predicting vascular complications in patients undergoing free flap reconstruction leveraging machine learning methods. METHODS: We reviewed the medical data of patients who underwent free flap reconstruction at the Affiliated Hospital of Zunyi Medical University retrospectively from January 1, 2019, to December 31, 2021. Statistical analysis was used to screen risk factors. A training data set was generated and augmented using the synthetic minority oversampling technique. Logistic regression, random forest and neural network, models were trained, using this dataset. The performance of these three predictive models was then evaluated and compared using a test set, with four metrics, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 570 patients who underwent free flap reconstruction were included in this study, 46 of whom developed postoperative vascular complications. Among the models tested, the neural network model exhibited superior performance on the test set, achieving an AUC of 0.828. Multivariate logistic regression analysis identified that preoperative hemoglobin levels, preoperative fibrinogen levels, operation duration, smoking history, the number of anastomoses, and peripheral vascular injury as statistically significant independent risk factors for vascular complications post-free flap reconstruction. The top five predictive factors in the neural network were fibrinogen content, operation duration, donor site, body mass index (BMI), and platelet count. CONCLUSION: Hemoglobin levels, fibrinogen levels, operation duration, smoking history, and anastomotic veins are independent risk factors for vascular complications following free flap reconstruction. These risk factors enhance the ability of machine learning models to predict the occurrence of vascular complications and identify high-risk patients. The neural network model outperformed the logistic regression and random forest models, suggesting its potential to aid clinicians in early identification of high-risk patients thereby mitigating patient suffering and improving prognosis.

Astroglial Activation Is Exacerbated in a Down Syndrome Mouse Model.

Down syndrome (DS), also known as trisomy 21, is one of the most common chromosomal disorders associated with intellectual disability. Mouse models are valuable for mechanistic and therapeutic intervention studies. The purpose of this study was to investigate astroglial anomalies in Dp16, a widely used DS mouse model. Brain sections were prepared from one-month-old Dp16 mice and their littermates, immunostained with an anti-GFAP or anti-S100B antibody, and imaged to reconstruct astroglial morphology in three dimensions. No significant difference in the number of astrocytes was found in either the hippocampal CA1 region or cortex between Dp16 and WT mice. However, the average astroglial volume in Dp16 was significantly (P < 0.05) greater than that in WT, suggesting the astroglial activation. Reanalysis of the single-nucleus RNA sequencing data indicated that the genes differentially expressed between WT and Dp16 astrocytes were associated with synapse organization and neuronal projection. In contrast, in vitro cultured neonatal astrocytes did not exhibit significant morphological changes. The expression of Gfap in in vitro cultured Dp16 astrocytes was not increased as it was in in vivo hippocampal tissue. However, after treatment with lipopolysaccharides, the inflammatory response gene IFNß increased significantly more in Dp16 astrocytes than in WT astrocytes. Overall, our results showed that the increase in astrogliogenesis in DS was not apparent in the early life of Dp16 mice, while astrocyte activation, which may be partly caused by increased responses to inflammatory stimulation, was significant. The inflammatory response of astrocytes might be a potential therapeutic target for DS intellectual disability.

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.