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Background. When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing. Materials and Methods. ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31. Results. HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing. Conclusion. Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.

Keratinocytes, the most important cell type constituting the epidermis, migrate to restore the epithelial barrier during wound healing and are a crucial step in wound healing. This study utilized bioinformatics analysis of comprehensive expression datasets of aberrantly expressed genes in wound healing to identify the abnormal expression of the critical transcription factor Fos-like antigen-1 (FOSL1), which is involved in various diseases. Currently, there is limited research on the role of FOSL1 in wound healing, and its molecular mechanisms remain unclear. This study explores the role and regulatory mechanisms of FOSL1 in the wound-healing process. A comprehensive expression dataset of abnormal genes in wound repair was constructed by bioinformatics analysis. Mouse trauma models and mouse wound splint models were constructed to verify the role of FOSL1 in vivo. Real-time quantitative polymerase chain reaction (qRT-PCR), immunoblot, immunofluorescence staining, and HE staining were used to confirm the analysis, and FOSL1 was used as the target in the wound healing process. At the cellular level, using 5ʹ-ethynyl-2ʹ-deoxyuridine (EdU) assay, Transwell assay, Migration assay, western blotting and immunofluorescence, FOSL1 promoted the molecular mechanism of wound repair by regulating the proliferation and migration of keratinocytes through IL-17 signaling pathway. Bioinformatics analysis revealed differential expression of FOSL1 during wound healing. In the mouse back wound model, qRT-PCR, western blotting (WB), and immunofluorescence staining showed significant upregulation of FOSL1 and IL-17 expression during wound tissue healing, indicating a close association between FOSL1 and mouse wound healing. In the mouse wound splinting model, subcutaneous injection of recombinant FOSL1 protein contributed to wound surface healing. Overexpression of FOSL1 in HaCaT cells promoted their proliferation and migration abilities. When IL-17 inhibitor was added to HaCaT cells, both FOSL1 overexpression and knockdown inhibited the proliferation and migration abilities of HaCaT cells. Thus, this study confirms that FOSL1 promotes keratinocyte proliferation and migration through the IL-17 signaling pathway, facilitating wound healing in epidermal wound repair. The results of this study indicate that FOSL1 plays a key role in epidermal wound healing, and elucidate a new molecular mechanism by which FOSL1 promotes keratinocyte proliferation and migration through IL-17 signaling pathway in epidermal wound repair, thereby promoting wound healing.

Rising studies have consistently reported gut bacteriome alterations in schizophrenia (SCZ). However, little is known about the role of the gut virome on shaping the gut bacteriome in SCZ. Here in, we sequenced the fecal virome, bacteriome, and host peripheral metabolome in 49 SCZ patients and 49 health controls (HCs). We compared the gut bacterial community composition and specific abundant bacteria in SCZ patients and HCs. Specific gut viruses and host peripheral metabolites co-occurring with differential bacteria were identified using Multiple Co-inertia Analysis (MCIA). Additionally, we construct a latent serial mediation model (SMM) to investigate the effect of the gut virome on SCZ through the bacteriome and host metabolic profile. SCZ patients exhibited a decreased gut bacterial β-diversity compared to HCs, with seven differentially abundant bacteria, including Coprobacillaceae , Enterococcaceae etc. Gut viruses including Suoliviridae and Rountreeviridae , co-occur with these SCZ-related bacteria. We found that the viral-bacterial transkingdom correlations observed in HCs were dramatically lost in SCZ. The altered correlations profile observed in SCZ may impact microbiota-derived peripheral metabolites enriched in the bile acids pathway, eicosanoids pathway, and others, contributing to host immune dysfunction and inflammation. The SMM model suggested potential causal chains between gut viruses and SCZ, indicating that the effect of gut virome on SCZ is significantly mediated by bacteriome and metabolites. In conclusion, these findings provide a comprehensive perspective on the role of gut microbiota in the pathogenesis of SCZ. They reveal that patients with schizophrenia harbor an abnormal virome-bacteriome ecology, shedding light on the potential development of microbial therapeutics.

Aim: Genome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about the genetic structure of BD subtypes. We aimed to investigate the genetic overlap and distinction of bipolar type I (BD I) & type II (BD II) by conducting integrative post-GWAS analyses. Methods: We utilized single nucleotide polymorphism (SNP)–level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis, including exploring the potential causal associations between two BD subtypes and lithium responses and comparing the difference in genetic structures among four different psychiatric traits. Results: SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184 , and RPL10AP3 , shared by BD I and II, and one locus ( MAD1L1 ) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes affecting BD I and II through expression in specific brain regions (nucleus accumbens for BD I). Cross-phenotype analyses indicated that BD I and II share continuous genetic structures with schizophrenia and major depressive disorder, which help fill the gaps left by the dichotomy of mental disorders. Conclusion: These combined evidences illustrate genetic convergence and divergence between BD I and II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.

We have successfully designed, fabricated, installed, and tested a super compact X -band SLAC Energy Doubler system at SLAC. It is composed of an elegant 3 dB coupler–mode converter–polarizer coupled to a single spherical energy storage cavity with high Q0 of 94000 and a diameter less than 12 cm. The available rf peak power of 50 MW can be compressed to a peak average power of more than 200 MW in order to double the kick for the electron bunches in a rf transverse deflector system and greatly improve the measurement resolution of both the electron bunches and the x-ray free-electron laser pulses. The design physics and fabrication as well as the measurement results will be presented in detail. High-power operation has demonstrated the excellent performance of this rf compression system without rf breakdown, sign of pulse heating, and rf radiation.

Astroblastoma is an uncommon tumor of the central nervous system. It is variable in morphology, but the astroblastic pseudorosettes and vascular hyalinization are the most important features. Most astroblastomas occur in the cerebral hemisphere. We report a recurrent high-grade astroblastoma with fusion in the spinal cord. Two lesions were found in the T5-7 level and T12-L1 level, and they were well defined in images. Rhabdoid and signet-ring-like cells were observed. It may be classified as a high-grade tumor due to cellularity, high mitotic count, and pleomorphism. The tumor cells were diffusely positive for GFAP, Olig-2, and S-100 protein. We found the MN1 arrangement and the loss of chromosome 1p by FISH, and further validated the BEN domain containing 2 genes ( ), which is the fusion partner of meningioma 1 gene ( ), by next-generation sequencing (NGS) and Sanger sequencing. The mutation is crucial in the diagnosis and prognosis of rare astroblastoma. The spinal cord astroblastoma may have a high recurrence rate because of the residual lesion at the unique location and higher grade; the connection with the gene mutation is unclear. Regular follow-up is necessary. Further study and more cases are needed to establish evidence for diagnosis, prognosis, and treatment of astroblastoma with molecular characteristics.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision. Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder. Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates. These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Major depressive disorder (MDD) and autoimmune thyroid disease (AITD) frequently co-occur, yet the genetic factors underlying their comorbidity remain unclear. We performed a population-matched cohort study from the UK Biobank to evaluate the phenotypic association between MDD and AITD. Genetic correlation, causal relationships, and pleiotropic loci/genes shared between the diseases were assessed based on common variants using genome-wide association study (GWAS) summary statistics, complemented by individual-level validation through polygenic risk score analysis. We additionally performed an exome-wide association analysis using the UK Biobank 450k whole-exome sequencing (WES) release to identify disease-specific risk genes from rare variants. Findings from common and rare variants were integrated and subjected to pathway enrichment, protein-protein interaction (PPI) and transcription factor (TF) analyses to locate functional modules. In the cohort study, MDD and AITD were associated with a 2.8-fold increased risk of developing the other condition. We confirmed a modest but statistically significant positive genetic correlation (r  = 0.14, P = 2.96 × 10 ) and confirmed the absence of a direct causal relationship. Integrative pleiotropy analyses identified 14 pleiotropic loci mapped to 58 shared genes. Gene ontology, TF enrichment and PPI analyses of disease-specific and shared genes revealed that the genetic signals converge on shared modules involving T-cell receptor signaling, thyroid hormone metabolic process and neurodegeneration, prioritized by key immune-inflammatory and neuro-developmental regulators. Our findings provide a molecular framework for MDD-AITD comorbidity, highlighting specific pathways as potential targets for integrated therapeutic strategies.

A comprehensive set of parallel finite-element codes suite ACE3P (Advanced Computational Electromagnetics 3D Parallel) is developed by SLAC for multi-physics modeling of particle accelerators running on massively parallel computer platforms for high fidelity and high accuracy simulation. ACE3P enables rapid virtual prototyping of accelerator and RF component design, optimization and analysis. Advanced modeling capabilities have been facilitated by implementations of novel algorithms for numerical solvers. Code performance on state-of-the-art high performance computing (HPC) platforms for large-scale RF modeling in accelerator applications will be presented in this paper. All the simulations have been performed on the supercomputers at National Energy Research Computer Center (NERSC).

Exposure to urban birth, childhood trauma, and lower Intelligence Quotient (IQ) were the most well-established risk factors for schizophrenia in developed countries. In developing countries, whether urban birth is a risk factor for schizophrenia and how these factors are related to one another remain unclear. This study aimed to investigate whether IQ mediates the relationship between urban birth or childhood trauma and first-episode schizophrenia (FES) in China. Birthplace, childhood trauma questionnaire (CTQ), and IQ were collected from 144 patients with FES and 256 healthy controls (HCs). Hierarchical logistic regression analysis was conducted to investigate the associations between birthplace, childhood trauma, IQ, and FES. Furthermore, mediation analysis was used to explore the mediation of IQ in the relationship between birthplace or childhood trauma and FES. After adjusting for age, sex and educational attainment, the final model identified urban birth (odds ratio (OR) = 3.15, 95% CI = 1.54, 6.44) and childhood trauma (OR = 2.79, 95% CI = 1.92, 4.06) were associated an elevated risk for FES. The 52.94% total effect of birthplace on the risk of FES could be offset by IQ (indirect effect/direct effect). The association between childhood trauma and FES could be partly explained by IQ (22.5%). In total, the mediation model explained 70.5% of the total variance in FES. Our study provides evidence that urban birth and childhood trauma are associated with an increased risk of FES. Furthermore, IQ mediates the relationship between urban birth or childhood trauma and FES.