Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Association of proton-density fat fraction with osteoporosis: a systematic review and meta-analysis.

This study aimed to evaluate the correlation between measuring proton-density fat fraction (PDFF) in bone marrow using multi-echo chemical shift-encoded MRI and osteoporosis, assessing its effectiveness as a biomarker for osteoporosis. A systematic review was conducted by two independent researchers using Cochrane, PubMed, EMBASE, and Web of Science databases up to December 2023. Quality assessments were evaluated using the Cochrane risk of bias tool and the Agency for Healthcare Research and Quality (AHRQ) checklist. Fourteen studies involving 1495 patients were analyzed. The meta-analysis revealed a significant difference in PDFF values between the osteoporosis/osteopenia group and the normal control group, with a mean difference of 11.04 (95% CI: 9.17 to 12.92, Z=11.52, P < 0.00001). Measuring PDFF via MRI shows potential as an osteoporosis biomarker and may serve as a risk factor for osteoporosis. This insight opens new avenues for future diagnostic and therapeutic strategies, potentially improving osteoporosis management and patient care. OBJECTIVE: This study aims to assess the correlation between measuring proton-density fat fraction (PDFF) in bone marrow using multi-echo chemical shift-encoded MRI and osteoporosis, evaluating its effectiveness as a biomarker for osteoporosis. MATERIALS AND METHODS: This systematic review was carried out by two independent researchers using Cochrane, PubMed, EMBASE, and Web of Science databases up to December 2023. Quality assessments were evaluated using the Cochrane risk of bias tool and the Agency for Healthcare Research and Quality (AHRQ) checklist. RESULTS: Fourteen studies involving 1495 patients were analyzed. The meta-analysis revealed a significant difference in PDFF values between the osteoporosis/osteopenia group and the normal control group, with a (MD = 11.04, 95% CI: 9.17 to 12.92, Z = 11.52, P < 0.00001). Subgroup analyses indicated that diagnostic methods, gender, and echo length did not significantly impact the PDFF-osteoporosis association. CONCLUSION: PDFF measurement via MRI shows potential as an osteoporosis biomarker and may serve as a risk factor for osteoporosis. This insight opens new avenues for future diagnostic and therapeutic strategies, potentially improving osteoporosis management and patient care.

The bioinformatics toolbox for circRNA discovery and analysis.

Circular RNAs (circRNAs) are a unique class of RNA molecule identified more than 40 years ago which are produced by a covalent linkage via back-splicing of linear RNA. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field of types and biological functions of circRNAs. In parallel with technological developments, practical applications of circRNAs have arisen including their utilization as biomarkers of human disease. Currently, circRNA-associated bioinformatics tools can support projects including circRNA annotation, circRNA identification and network analysis of competing endogenous RNA (ceRNA). In this review, we collected about 100 circRNA-associated bioinformatics tools and summarized their current attributes and capabilities. We also performed network analysis and text mining on circRNA tool publications in order to reveal trends in their ongoing development.

Development of a novel MR-conditional microwave needle for MR-guided interventional microwave ablation at 1.5T.

PURPOSE: To develop an MR-conditional microwave needle that generates a spherical ablation zone and clear MRI visibility for MR-guided microwave ablation. METHODS: An MR-conditional microwave needle consisting of zirconia tip and TA18 titanium alloy tube was investigated. The numerical model was created to optimize the needle's geometry and analyze its performance. A geometrically optimized needle was produced using non-magnetic materials based on the electromagnetics simulation results. The needle's mechanical properties were tested per the Chinese pharmaceutical industry standard YY0899-2013. The MRI visibility performance and ablation characteristics of the needle was tested both in vitro (phantom) and in vivo (rabbit) at 1.5T. The RF-induced heating was evaluated in ex vivo porcine liver. RESULTS: The needle's mechanical properties met the specified requirements. The needle susceptibility artifact was clearly visible both in vitro and in vivo. The needle artifact diameter (A) was small in in vivo (Ashaft: 4.96 ± 0.18 mm for T1W-FLASH, 3.13 ± 0.05 mm for T2-weighted fast spin-echo (T2W-FSE); Atip: 2.31 ± 0.09 mm for T1W-FLASH, 2.29 ± 0.08 mm for T2W-FSE; tip location error [TLE]: -0.94 ± 0.07 mm for T1W-FLASH, -1.10 ± 0.09 mm for T2W-FSE). Ablation zones generated by the needle were nearly spherical with an elliptical aspect ratio ranging from 0.79 to 0.90 at 30 W, 50 W for 3, 5, 10 min duration ex vivo ablations and 0.86 at 30 W for 10 min duration in vivo ablations. CONCLUSION: The designed MR-conditional microwave needle offers excellent mechanical properties, reliable MRI visibility, insignificant RF-induced heating, and a sufficiently spherical ablation zone. Further clinical development of MR-guided microwave ablation appears warranted.

Trends in the development of miRNA bioinformatics tools.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression via recognition of cognate sequences and interference of transcriptional, translational or epigenetic processes. Bioinformatics tools developed for miRNA study include those for miRNA prediction and discovery, structure, analysis and target prediction. We manually curated 95 review papers and ∼1000 miRNA bioinformatics tools published since 2003. We classified and ranked them based on citation number or PageRank score, and then performed network analysis and text mining (TM) to study the miRNA tools development trends. Five key trends were observed: (1) miRNA identification and target prediction have been hot spots in the past decade; (2) manual curation and TM are the main methods for collecting miRNA knowledge from literature; (3) most early tools are well maintained and widely used; (4) classic machine learning methods retain their utility; however, novel ones have begun to emerge; (5) disease-associated miRNA tools are emerging. Our analysis yields significant insight into the past development and future directions of miRNA tools.

The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.

PURPOSE: Colon cancer (CC) is a very common gastrointestinal tumor that is prone to invasion and metastasis in the late stage. This study aims to observe the expression of Na+/Ca2+ exchangers (NCXs) and analyze the correlation between NCXs and the prognosis of CC. METHODS: Specimens of 111 stage II-IV CC patients were collected. We used western blotting, qPCR, and immunohistochemical staining to observe the distributions and expression levels of NCX isoforms (NCX1, NCX2, and NCX3) in CC and distal normal tissues. Cox proportional hazards models were used to assess prognostic factors for patients. RESULTS: The expression of NCXs in most tumor specimens was lower than that in normal tissues. The NCX expression levels in tumor tissues from the primary tumor, local lymph node metastasis sites, and distant liver metastasis sites were increasingly significantly lower than those in normal tissues. The results of the Kaplan-Meier survival curves showed that the downregulation of any NCX isoform was closely related to the worse prognosis of advanced CC. CONCLUSION: NCXs can be used as independent prognostic factors for CC. Our research results are expected to provide new targets for the treatment of CC.

Evaluation of the Risk Prediction Tools for Patients With Coronavirus Disease 2019 in Wuhan, China: A Single-Centered, Retrospective, Observational Study.

OBJECTIVES: To evaluate and compare the efficacy of National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment on predicting in-hospital death in patients with coronavirus disease 2019. DESIGN: A retrospective, observational study. SETTING: Single center, West Campus of Wuhan Union hospital-a temporary center to manage critically ill patients with coronavirus disease 2019. PATIENTS: A total of 673 consecutive adult patients with coronavirus disease 2019 between January 30, 2020, and March 14, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demography, comorbidities, vital signs, mental status, oxygen saturation, and use of supplemental oxygen at admission to the ward were collected from medical records and used to score National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Total number of patients was 673 (51% male) and median (interquartile range) age was 61 years (50-69 yr). One-hundred twenty-one patients died (18%). For predicting in-hospital death, the area under the receiver operating characteristics (95% CI) for National Early Warning Score, National Early Warning Score 2, Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment were 0.882 (0.847-0.916), 0.880 (0.845-0.914), 0.839 (0.800-0.879), 0.766 (0.718-0.814), and 0.694 (0.641-0.746), respectively. Among the parameters of National Early Warning Score, the oxygen saturation score was found to be the most significant predictor of in-hospital death. The area under the receiver operating characteristic (95% CI) for oxygen saturation score was 0.875 (0.834-0.916). CONCLUSIONS: In this single-center study, the discrimination of National Early Warning Score/National Early Warning Score 2 for predicting mortality in patients with coronavirus disease 2019 admitted to the ward was found to be superior to Rapid Emergency Medicine Score, Confusion, Respiratory rate, Blood pressure, Age 65 score, and quick Sepsis-related Organ Failure Assessment. Peripheral oxygen saturation could independently predict in-hospital death in these patients. Further validation of our finding in multiple settings is needed to determine its applicability for coronavirus disease 2019.

A novel approach for the forensic diagnosis of drowning by microbiological analysis with next-generation sequencing and unweighted UniFrac-based PCoA.

The diagnosis of drowning is one of the major challenges in forensic practice, especially when the corpse is in a state of decomposition. Novel indicators of drowning are desired in the field of forensic medicine. In the past decade, aquatic bacteria have attracted great attention from forensic experts because they can easily enter the blood circulation with drowning medium, and some of them can proliferate in the corpse. Recently, the advent of next-generation sequencing (NGS) has created new opportunities to efficiently analyze whole microbial communities and has catalyzed the development of forensic microbiology. We presumed that NGS could be a potential method for diagnosing drowning. In the present study, we verified this hypothesis by fundamental experiments in drowned and postmortem-submersed rat models. Our study revealed that detecting the bacterial communities with NGS and processing the data in a transparent way with unweighted UniFrac-based principal coordinates analysis (PCoA) could clearly discriminate the skin, lung, blood, and liver specimens of the drowning group and postmortem submersion group. Furthermore, the acquired information could be used to identify new cases. Taken together, these results suggest that we could build a microbial database of drowned and postmortem-submersed victims by NGS and subsequently use a bioinformatic method to diagnose drowning in future forensic practice.

ViRBase: a resource for virus-host ncRNA-associated interactions.

Increasing evidence reveals that diverse non-coding RNAs (ncRNAs) play critically important roles in viral infection. Viruses can use diverse ncRNAs to manipulate both cellular and viral gene expression to establish a host environment conducive to the completion of the viral life cycle. Many host cellular ncRNAs can also directly or indirectly influence viral replication and even target virus genomes. ViRBase (http://www.rna-society.org/virbase) aims to provide the scientific community with a resource for efficient browsing and visualization of virus-host ncRNA-associated interactions and interaction networks in viral infection. The current version of ViRBase documents more than 12,000 viral and cellular ncRNA-associated virus-virus, virus-host, host-virus and host-host interactions involving more than 460 non-redundant ncRNAs and 4400 protein-coding genes from between more than 60 viruses and 20 hosts. Users can query, browse and manipulate these virus-host ncRNA-associated interactions. ViRBase will be of help in uncovering the generic organizing principles of cellular virus-host ncRNA-associated interaction networks in viral infection.

[Research on Identification of Organic Gunshot Residue with Micro-Raman Spectroscopy].

A rapid approach for the nondestructive, accurate detection of organic gunshot residue was investigated. Raman microscopy was used to identify organic gunshot residue and the propellant in ammunition. The optimal excitation wavelength for the detection of organic particles using Raman spectroscopy was 473 nm. The Raman spectra of organic gunshot residue obtained using 473 nm laser excitation can effectively avoid the interference of fluorescence. The results demonstrated that the organic particles were mainly from the partially burned propellant particles. Meanwhile it was proved that the main component was basically consistent with the propellant except somehow damage in chemical structure or degree of crystallization with Raman spectra. The surface color of organic particles was mainly brassiness, dark gray. A lot of craters were distributed on the surface of organic particles. Spherical inorganic particles with metallic luster attached to the surface of organic particles can be regarded as the typical characteristics of gunshot residue.

Overexpressed FKBP5 mediates colorectal cancer progression and sensitivity to FK506 treatment via the NF-κB signaling pathway.

Colorectal cancer (CRC) is a common and deadly tumor. FK506-binding protein 5 (FKBP5) is associated with some cancers, but the role of FKBP5 in CRC is not clear. The present study aimed to reveal the relationship between FKBP5 and CRC and to uncover the roles of FK506 in CRC. In total, 96 CRC patients were recruited. Survival analysis was conducted using the Kaplan-Meier method and COX regression analyses. Bioinformatics analyses were performed to explore the functions of FKBP5. The mechanisms of FKBP5 and the roles of FK506 in CRC progression were clarified by immunohistochemistry, MTS, scratch assay, transwell and flow cytometric analyses via in vitro and in vivo experiments. FKBP5 was overexpressed in 77 cancer tissues compared to that in matched normal tissues, and the overall survival rate of these patients was relatively shorter. Bioinformatics analyses showed that FKBP5 regulates proliferation, invasion, migration, epithelial-mesenchymal transition and nuclear factor-kappa B (NF-κB) signaling. The upregulation or downregulation of FKBP5 dramatically increases or decreases the proliferation, invasion and migration abilities of CRC cells. The expression of NF-κB, inhibitor B kinase α, matrix metalloproteinase-2 and metalloproteinase-9 positively correlated with FKBP5. FK506 inhibits the progression of CRC via the FKBP5/NF-κB signaling pathway. Our study identified a regulatory role for FKBP5 in CRC progression. Therefore, targeting FKBP5 may provide a novel treatment approach for CRC. FK506 can inhibit the progression of CRC by restraining the FKBP5/NF-κB signaling pathway and is expected to become a new drug for the treatment of CRC.

An unrolled neural network for accelerated dynamic MRI based on second-order half-quadratic splitting model.

The reconstruction of dynamic magnetic resonance images from incomplete k-space data has sparked significant research interest due to its potential to reduce scan time. However, traditional iterative optimization algorithms fail to faithfully reconstruct images at higher acceleration factors and incur long reconstruction time. Furthermore, end-to-end deep learning-based reconstruction algorithms suffer from large model parameters and lack robustness in the reconstruction results. Recently, unrolled deep learning models, have shown immense potential in algorithm stability and applicability flexibility. In this paper, we propose an unrolled deep learning network based on a second-order Half-Quadratic Splitting(HQS) algorithm, where the forward propagation process of this framework strictly follows the computational flow of the HQS algorithm. In particular, we propose a degradation-sense module by associating random sampling patterns with intermediate variables to guide the iterative process. We introduce the Information Fusion Transformer(IFT) to extract both local and non-local prior information from image sequences, thereby removing aliasing artifacts resulting from random undersampling. Finally, we impose low-rank constraints within the HQS algorithm to further enhance the reconstruction results. The experiments demonstrate that each component module of our proposed model contributes to the improvement of the reconstruction task. Our proposed method achieves comparably satisfying performance to the state-of-the-art methods and it exhibits excellent generalization capabilities across different sampling masks. At the low acceleration factor, there is a 0.7% enhancement in the PSNR. Furthermore, when the acceleration factor reached 8 and 12, the PSNR achieves an improvement of 3.4% and 5.8% respectively.

Unusual coexistence: branchial cleft cyst harboring papillary thyroid carcinoma with lymph node metastasis - a rare case report and clinical insights.

Background: The simultaneous occurrence of Branchial Cleft Cyst (BCC) and Papillary Thyroid Carcinoma (PTC) represents an unusual malignant tumor, with cases featuring associated lymph node metastasis being particularly rare. This combination underscores an increased potential for metastasis, and the assessment of neck masses, particularly on the lateral aspect, may inadvertently overlook the scrutiny of the thyroid. Therefore, healthcare providers should exercise vigilance, especially in patients over the age of 40, regarding the potential for neck masses to signify metastasis from thyroid malignancies. Currently, surgical intervention stands as the primary effective curative method, while the postoperative administration of radioactive iodine therapy remains a topic of ongoing debate. Case report: In the presented case, a 48-year-old male patient with a right neck mass underwent surgical intervention. The procedure included the excision of the right neck mass, unilateral thyroidectomy with isthmus resection, and functional neck lymph node dissection under tracheal intubation and general anesthesia. Postoperative pathology findings revealed the coexistence of a BCC with metastatic PTC in the right neck mass, as well as papillary carcinoma in the right thyroid lobe. Lymph node metastasis was observed in the central and levels III of the right neck. Conclusion: The rare amalgamation of a BCC with PTC and concurrent lymph node metastasis underscores the invasive nature of this malignancy. Healthcare professionals should be well-acquainted with its clinical presentation, pathological characteristics, and diagnostic criteria. A multidisciplinary approach is strongly recommended to enhance patient outcomes.

Angiosarcoma of the breast: A review.

Breast angiosarcoma is a rare and highly aggressive malignancy with a poor prognosis. It can occur spontaneously or be associated with factors such as radiation therapy or chronic lymphedema. The etiology and pathogenesis of this disease are still unclear, the clinical symptoms and imaging findings lack specificity, and the pathological morphology is diverse, which is easy to be confused with other diseases. There is no clear guideline for surgical treatment. Although the optimal surgical approach remains unclear, the ultimate goal is surgical excision with optimal margins, which remains the primary method of treatment. In clinical practice, the choice of the surgical approach should be made by considering the tumor size, pathological type, and patient preferences. In clinical practice, the selection of surgical methods should be carried out with comprehensive consideration of tumor size, pathological types and patients' wishes. There is no clear consensus on whether radiotherapy and chemotherapy should be carried out after surgery, and its optimal program and efficacy are uncertain. This article reviews the etiology, clinical manifestations, pathological features, imaging findings, treatment, prognosis and other aspects of breast angiosarcoma, so as to strengthen clinicians' overall understanding of this disease and avoid missed diagnosis and misdiagnosis.

The feasibility and clinical significance of lateral approach thyroidectomy.

BACKGROUND: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. METHODS: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. RESULTS: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. CONCLUSION: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

A novel method for highly linear gradient coil design based on stream function.

BACKGROUND: Magnetoencephalography (MEG) and magnetic resonance imaging (MRI) are non-invasive imaging techniques that offer effective means for disease diagnosis. A more straightforward and optimized method is presented for designing gradient coils which are pivotal parts of the above imaging systems. PURPOSE: A novel design method based on stream function combining an optimization algorithm is proposed to obtain highly linear gradient coil. METHODS: Two-dimensional Fourier expansion of the current field on the surface where the coil is located and the equipotential line of the expansion term superposition according to the number of turns of the coil are used to represent the coil shape. Particle swarm optimization is utilized to optimize the coil shape while linearity and field uniformity are used as parameters to evaluate the coil performance. Through this method, the main parameters such as input current distribution region, coil turns, desired magnetic field strength, expansion order and iteration times can be combined in a given solution space to optimize coil design. RESULTS: Simulation results show that the maximum linearity spatial deviation of the designed bi-planar x-gradient coil compared with that of target field method is reduced from 14% to 0.54%, and that of the bi-planar z-gradient coil is reduced from 8.98% to 0.52%. Similarly, that of the cylindrical x-gradient coil is reduced from 2% to 0.1%, and that of the cylindrical z-gradient coil is reduced from 0.87% to 0.45%. The similar results are found in the index of inhomogeneity error. Moreover, it has also been verified experimentally that the result of measured magnetic field is consist with simulated result. CONCLUSIONS: The proposed method provides a straightforward way that simplifies the design process and improves the linearity of designed gradient coil, which could be beneficial to realize better magnetic field in engineering applications.

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Complexin-1 enhances ultrasound neurotransmission in the mammalian auditory pathway.

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.

Prenatal alcohol exposure enhanced alcohol preference and susceptibility to PTSD in a sex-dependent manner through the synaptic HCN1 channel.

BACKGROUND: Prenatal alcohol exposure (PAE) adversely affects the neurobiological and behavioral functions of offspring. Increasing evidence indicates that alcohol-use disorders and post-traumatic stress disorder (PTSD) commonly co-occur. Enhanced function of hyperpolarization-activated gated channel 1 (HCN1) may be involved in the pathogenesis of PTSD. This study aimed to explore the effect of PAE on fear extinction, spontaneous recovery, alcohol preference, and function of HCN1 channels in offspring of both sexes. METHODS: The PAE model was established with a 20 % (m/V) ethanol solution, and offspring were treated with 0.5, 1, and 2 µg/mL ZD7288 to block the HCN1 channel. Behavioral tests were used to detect the mental state and fear of extinction of the mice. Western blot was used to detect HCN1 expression in the synaptosomes. The BDNF/TrkB-pmTOR pathway was also examined. RESULTS: ZD7288 administration ameliorated PAE-induced impairment of fear extinction and depression-like behavior. ZD7288 administration also alleviated PAE-induced inhibition of the HCN1 channel in the prefrontal cortex (PFC) and the BDNF/TrkB-pmTOR pathway in the hippocampus of offspring. In addition, the therapeutic effect of ZD7288 in males was better than that in females. CONCLUSIONS: Overall, these results suggest that PAE enhances alcohol preference and susceptibility to PTSD through synaptic HCN1 channels in the PFC. In addition, ZD7288 may be a promising candidate for preventing alcohol-associated PTSD-like syndrome, particularly in males. LIMITATIONS: The effects of ZD7288 were only studied in PAE animals and not in healthy animals.

Multilayer brain network modeling and dynamic analysis of juvenile myoclonic epilepsy.

Objective: It is indisputable that the functional connectivity of the brain network in juvenile myoclonic epilepsy (JME) patients is abnormal. As a mathematical extension of the traditional network model, the multilayer network can fully capture the fluctuations of brain imaging data with time, and capture subtle abnormal dynamic changes. This study assumed that the dynamic structure of JME patients is abnormal and used the multilayer network framework to analyze the change brain community structure in JME patients from the perspective of dynamic analysis. Methods: First, functional magnetic resonance imaging (fMRI) data were obtained from 35 JME patients and 34 healthy control subjects. In addition, the communities of the two groups were explored with the help of a multilayer network model and a multilayer community detection algorithm. Finally, differences were described by metrics that are specific to the multilayer network. Results: Compared with healthy controls, JME patients had a significantly lower modularity degree of the brain network. Furthermore, from the level of the functional network, the integration of the default mode network (DMN) and visual network (VN) in JME patients showed a significantly higher trend, and the flexibility of the attention network (AN) also increased significantly. At the node level, the integration of seven nodes of the DMN was significantly increased, the integration of five nodes of the VN was significantly increased, and the flexibility of three nodes of the AN was significantly increased. Moreover, through division of the core-peripheral system, we found that the left insula and left cuneus were core regions specific to the JME group, while most of the peripheral systems specific to the JME group were distributed in the prefrontal cortex and hippocampus. Finally, we found that the flexibility of the opercular part of the inferior frontal gyrus was significantly correlated with the severity of JME symptoms. Conclusion: Our findings indicate that the dynamic community structure of JME patients is indeed abnormal. These results provide a new perspective for the study of dynamic changes in communities in JME patients.