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The combination of education and robots is becoming an increasingly important issue. Although researchers have conducted some studies on educational robotics in STEM education at the undergraduate level, no research examined the effects of gamified educational robotics on participants' motivation and creativity. Therefore, this study examines the effects of gamified educational robots on participants' learning motivation and creativity in STEM. A quasi-experimental research design was used in this study. A total of 108 students from two classes enrolled in the information technology course were involved as participants. Learning motivation and creativity scales were used to collect data. The participants were introduced to a gamified educational robot as the course objective, learning content, and game mechanism to increase motivation and help students solve problems. In contrast, students in the control group received conventional instruction consisting of group discussions and lectures. Activities in both groups were held for eighteen weeks in three phases. The results showed that gamified educational robots could enhance learning motivation and positively influence learners' creativity. The results also indicate that learning motivation has significant effects on creativity, and students with high motivation perform better in terms of creativity. The results strengthen interdisciplinary STEM teaching and promote students' learning outcomes.

Alternaria tenuissima (Kunze) Wiltshire 1933 is a plant pathogenic fungus mainly causing leaf blotch disease. Here, we de novo assembled mitochondrial genome of A. tenuissima isolate AT-1224. The total mitogenome size is 57,475 bp with 29.00% G + C content. The genome contained 12 coding genes and 15 hypothetical proteins, 34 transfer RNA (tRNA) genes and 2 ribosomal RNA (rRNA). There are 227 SSR repeats, range from 2 to 4 base pairs, most five repeats were AT (144), AAT (54), AG (33), AC (13) and AAG (5). The results also found 13 tandem repeats (>100 bp), the largest repeat were forward 2 times located from 13,405 to 20,024 bp and 25,549 to 32,168 bp. Phylogenetic analysis based on 17 species complete mitogenomes indicated that A. tenuissima mitogenome was closest to 2 species, A. solani and A. alternata, sister clade to 6 species, representing Curvularia clavate, Exserohilum rostratum, Exserohilum turcicum, Bipolaris cookie, Bipolaris oryzae and Bipolaris sorokiniana. Further analysis among common fungus in local apple orchards using mitochondrial protein-coding genes revealed A. tenuissima were closing to 2 Alternaria fungi and a fungus representing Phoma sp. These results provide a basic reference for identification and evolution studies of A. tenuissima on apple trees.

Guided by a participatory culture-specific consultation model, this study contributes to an understanding of the effectiveness of school consultation with teachers of refugee students. The goal of the present study was to determine the impact of an individual consultation intervention with refugee teachers on their self-efficacy and self-care, in addition to their peer consultation skills. The participants were 109 teachers at refugee schools in Malaysia, most of whom were refugees (91% refugees; 73% female). Of the 109 participants, 84 teachers were coconsultants with psychology graduate students; all 109 were individual consultees. The study used a two-timepoint design with the outcomes of self-reported teacher self-care; teacher self-efficacy in the management of refugee student emotion regulation and emotional engagement; and consultation skills. Additionally, consultee-reported goal attainment, consultation effectiveness, and satisfaction were collected. The findings suggested significant latent growth from baseline to post-intervention in refugee teacher self-care and self-efficacy in the management of student emotion regulation and emotional engagement in addition to the growth of their consultation skills. The effect sizes were large for latent growth of teacher self-efficacy in promoting student emotion regulation, behavior, and emotional engagement (d = 1.19, 1.01, 1.02); the effect size for self-care was medium (d = 0.62). Growth was not dependent on dosage, age, gender, or consultee education, with the exception of teacher self-efficacy in management of emotional engagement which was dependent on dosage. After the intervention, the consultees reported that they completed their consultation goals at a higher level than expected, were satisfied with the consultation, and found the consultants to be helpful. The discussion situates the findings in relevant theory, research, and the culture-specific context.

The remarkable advancements in technology have affected the way people engage, work, and learn. Digital literacy, also known as virtual learning, has the potential to improve lifelong learning. Workplace skills evolve at such a rapid pace that no school system can keep up with the continual need to alter how we work and live. Most crucially, our society's profound changes require young people to acquire new abilities. Malaysia has a long-term vision that calls for sustainable and productivity-driven growth that can only be accomplished with digitally literate employees. Although to some extent Malaysia education system has been initiating, there is very limited research that focuses on what drives digital literacy. There is no proper framework or guidelines that can be used as a blueprint to prepare the young graduates in the 21st-century workforce. The purpose of the study is to examine the drivers of digital literacy that can be taught in higher institutions and apply in today's digital workplace. This research focused on young adults as a unit of analysis and a quantitative method was used to collect the data. A total of 300 young individuals responded through self-administered questionnaires. The finding of the research showed that critical skills, operational skills, visual learning style, collaborative learning style and learning system enhance digital literacy. Finding further recommend that digital literacy improve both academic performance and employability. From this research, solutions can be proposed to both academicians and employers in achieving the digital literate graduates for the 21st-century workforce.

Abstract Toll/interleukin-1 receptor (TIR) domain-containing proteins play a critical role in immune responses in diverse organisms, but their function in bacterial systems remains to be fully elucidated. This study, focusing on Escherichia coli, addresses how TIR domain-containing proteins contribute to bacterial immunity against phage attack. Through an exhaustive survey of all E. coli genomes available in the NCBI database and testing of 32 representatives of the 90% of the identified TIR domain-containing proteins, we found that a significant proportion (37.5%) exhibit antiphage activities. These defense systems recognize a variety of phage components, thus providing a sophisticated mechanism for pathogen detection and defense. This study not only highlights the robustness of TIR systems in bacterial immunity, but also draws an intriguing parallel to the diversity seen in mammalian Toll-like receptors (TLRs), enriching our understanding of innate immune mechanisms across life forms and underscoring the evolutionary significance of these defense strategies in prokaryotes.

Abstract The purple leaves of Brassica napus are abundant in anthocyanins, which are renowned for their role in conferring distinct colors, stress tolerance, and health benefits, however the genetic basis of this trait in B. napus remains largely unelucidated. Herein, the purple leaf B. napus (PL) exhibited purple pigments in the upper epidermis and a substantial increase in anthocyanin accumulation, particularly of cyanidin, compared to green leaf B. napus (GL). The genetic control of the purple leaf trait was attributed to a semi-dominant gene, pl, which was mapped to the end of chromosome A03. However, sequencing of the fragments amplified by the markers linked to pl indicated that they were all mapped to chromosome B05 from B. juncea. Within this B05 chromosomal segment, the BjMYB113 gene-specific marker showed perfect co-segregation with the purple leaf trait in the F2 population, suggesting that the BjMYB113 introgression from B. juncea was the candidate gene for the purple leaf trait in B. napus. To further verify the function of candidate gene, CRISPR/Cas9 was performed to knock out the BjMYB113 gene in PL. The three myb113 mutants exhibited evident green leaf phenotype, absence of purple pigments in the adaxial epidermis, and a significantly reduced accumulation of anthocyanin compared to PL. Additionally, the genes involved in positive regulatory (TT8), late anthocyanin biosynthesis (DFR, ANS, UFGT), as well as transport genes (TT19) were significantly suppressed in the myb113 mutants, further confirming that BjMYB113 was response for the anthocyanin accumulation in purple leaf B. napus. This study contributes to an advanced understanding of the regulation mechanism of anthocyanin accumulation in B. napus.

Abstract Swine enteric coronaviruses (SeCoVs) pose a significant threat to the global pig industry, but no effective drugs are available for treatment. Previous research has demonstrated that thapsigargin (TG), an ER stress inducer, has broad-spectrum antiviral effects on human coronaviruses. In this study, we investigated the impact of TG on transmissible gastroenteritis virus (TGEV) infection using cell lines, porcine intestinal organoid models, and piglets. The results showed that TG effectively inhibited TGEV replication both in vitro and ex vivo. Furthermore, animal experiments demonstrated that oral administration of TG inhibited TGEV infection in neonatal piglets and relieved TGEV-associated tissue injury. Transcriptome analyses revealed that TG improved the expression of the ER-associated protein degradation (ERAD) component and influenced the biological processes related to secretion, nutrient responses, and epithelial cell differentiation in the intestinal epithelium. Collectively, these results suggest that TG is a potential novel oral antiviral drug for the clinical treatment of TGEV infection, even for infections caused by other SeCoVs.

Abstract Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, bla CTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.

Abstract Radish exhibits significant variation in color, particularly in sprouts, leaves, petals, fleshy roots, and other tissues, displaying a range of hues such as green, white, red, purple, and black. Although extensive research has been conducted on the color variation of radish, the underlying mechanism behind the variation in radish flower color remains unclear. To date, there is a lack of comprehensive research investigating the variation mechanism of radish sprouts, leaves, fleshy roots, and flower organs. This study aims to address this gap by utilizing transcriptome sequencing to acquire transcriptome data for white and purple radish flowers. Additionally, the published transcriptome data of sprouts, leaves, and fleshy roots were incorporated to conduct a systematic analysis of the regulatory mechanisms underlying anthocyanin biosynthesis in these four radish tissues. The comparative transcriptome analysis revealed differential expression of the anthocyanin biosynthetic pathway genes DFR, UGT78D2, TT12 and CPC in the four radish tissues. Additionally, the WGCNA results identified RsDFR.9c and RsUGT78D2.2c as hub genes responsible for regulating anthocyanin biosynthesis. By integrating the findings from the comparative transcriptome analysis, WGCNA, and anthocyanin biosynthetic pathway-related gene expression patterns, it is hypothesized that genes RsDFR.9c and RsUGT78D2.2c may serve as pivotal regulators of anthocyanins in the four radish tissues. Furthermore, the tissue-specific expression of the four copies of RsPAP1 is deemed crucial in governing anthocyanin synthesis and accumulation. Our results provide new insights into the molecular mechanism of anthocyanin biosynthesis and accumulation in different tissues of radish.

Abstract Background Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. Methods The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. Results We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. Conclusion Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.

Diploid lines (2n = 2x = 24) derived from tetraploid potato cultivars have been utilized to hybridize with wild diploid potato species, yielding fertile offsprings. Utilizing the pollen of Solanum tuberosum Group Phureja, such as IVP101, IVP35 and IVP48, as an inducer for wide hybridization with tetraploid cultivars represents a common method for producing diploids. In this study, we created a distant hybridization induced population of tetraploid potato cultivar Cooperation 88 (C88) and IVP101, and screened all diploids using flow cytometry and ploidyNGS. We investigated the genetic composition of chloroplast and nuclear genomes in 43 diploid offsprings. We found that all diploid offsprings share the same chloroplast genomic sequence as C88 and no evidence of paternal chloroplast inheritance was found. Used SNP data to calculate the theoretical introgression index of IVP101 with diploid offsprings. The results showed that the inducer’s nuclear genome was involved in the nuclear genome of the diploid offsprings with purple stem trait, indicating that the inducer nuclear genome was not completely eliminated in the nuclear genome during distant hybridization. Furthermore, we conducted a comparative analysis of the chloroplast genomes of the Solanum genus. The results indicated that (1) the chloroplast genome sizes of the 14 Solanum species ranged from 154,289 bp to 155,614 bp, with a total number of genes ranging 128-141, and with ycf1 and rps19 pseudogenes appearing at the IRB/SSC and IRA/LSC boundaries, respectively; (2) eight divergent hotspots distributed in the LSC and SSC regions of the Solanum chloroplast genomes were identified; (3) positive selection was detected in the clpP, rbcL, rps15, and rps4 genes, likely contributing to the adaptation of Solanum species to different habitats. These results reveal the variation and evolutionary characteristics of chloroplast genomes in Solanum plants.

BackgroundThe relationship of systolic blood pressure variability (SBPV) with Alzheimer’s disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions.MethodsLongitudinal data across 96 months (T0 to T4) were derived from the Alzheimer’s disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years).ResultsParticipants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008).ConclusionThese findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health.

Intestinal organoids are valuable tools for investigating intestinal physiology and pathology ex vivo. In previous studies, intestinal organoids of commercial pigs have been developed. Here, we established intestinal organoids derived from Wuzhishan miniature pigs (WZS pigs), a unique kind of pig in the Hainan province of China. Three-dimensional (3D) intestinal organoids and organoid monolayers were developed and assessed. Furthermore, the susceptibility of organoid monolayers of WZS pigs to transmissible gastroenteritis virus (TGEV) was demonstrated. An RNA-seq analysis revealed that the TGEV infection stimulated antiviral and inflammatory immune responses in organoid monolayer models. The study implied the transmission risk of swine enteric coronavirus on WZS pigs and provided useful tools for further research on WZS pigs as laboratory miniature pig models.

Neoadjuvant therapy followed by surgery is a common clinical strategy for operable non-small cell lung cancer (NSCLC), and the mainstream neoadjuvant therapies include chemoimmunotherapy, targeted therapy, and chemotherapy. However, there is a lack of studies to report the difference in benefits between these treatment modalities in the same institution. Therefore, this study aimed to depict the short-term efficacy of radiology and pathology achieved by different therapies and their impact on long-term survival as well as the underlying clinical significance. A total of 243 NSCLC patients who underwent different neoadjuvant therapies were eligible for inclusion. Demographic, radiological, and pathological features of patients were recorded. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. The objective response rates (ORR) of primary tumor in the chemoimmunotherapy, targeted therapy, and chemotherapy cohorts were 48.95 %, 57.58 %, and 34.09 % respectively, major pathological response (MPR) rates were 58.74 %, 15.15 %, and 20.83 % (P

High-grade serious ovarian cancer (HGSOC) is an aggressive malignancy that remains refractory to current immunotherapies. While advanced stage disease has been extensively studied, the cellular and molecular mechanisms that promote early immune escape in HGSOC remain largely unexplored. Here, we report that primary HGSO tumors program neutrophils to inhibit T cell anti-tumor function by activating the endoplasmic reticulum (ER) stress sensor IRE1α. We found that intratumoral neutrophils exhibited overactivation of ER stress response markers compared with their counterparts at non-tumor sites. Selective deletion of IRE1α in neutrophils delayed primary ovarian tumor growth and extended the survival of mice with HGSOC by enabling early T cell-mediated tumor control. Notably, loss of IRE1α in neutrophils sensitized tumor-bearing mice to PD-1 blockade, inducing HGSOC regression and long-term survival in ~ 50% of the treated hosts. Hence, neutrophil-intrinsic IRE1α facilitates early adaptive immune escape in HGSOC and targeting this ER stress sensor might be used to unleash endogenous and immunotherapy-elicited immunity that controls metastatic disease.

Brassica napus is one of the most important oil crops in the world. Breeding oilseed rape with colorful flowers can greatly enhance the ornamental value of B. napus and thus improve the economic benefits of planting. As water-soluble flavonoid secondary metabolites, anthocyanins are very important for the synthesis and accumulation of pigments in the petals of plants, giving them a wide range of bright colors. Despite the documentation of over 60 distinct flower shades in B. napus, the intricacies underlying flower color variation remain elusive. Particularly, the mechanisms driving color development across varying flower color backgrounds necessitate further comprehensive investigation. This research undertook a comprehensive exploration through the integration of transcriptome and metabolome analyses to pinpoint pivotal genes and metabolites underpinning an array of flower colors, including beige, beige-red, yellow, orange-red, deep orange-red, white, light-purple, and purple. First, we used a two-way BLAST search to find 275 genes in the reference genome of B. napus Darmor v10 that were involved in making anthocyanins. The subsequent scrutiny of RNA-seq outcomes underscored notable upregulation in the structural genes F3H and UGT, alongside the MYB75, GL3, and TTG1 transcriptional regulators within petals, showing anthocyanin accumulation. By synergizing this data with a weighted gene co-expression network analysis, we identified CHS, F3H, MYB75, MYB12, and MYB111 as the key players driving anthocyanin synthesis in beige-red, orange-red, deep orange-red, light-purple, and purple petals. By integrating transcriptome and weighted gene co-expression network analysis findings with anthocyanin metabolism data, it is hypothesized that the upregulation of MYB75, which, in turn, enhances F3H expression, plays a pivotal role in the development of pigmented oilseed rape flowers. These findings help to understand the transcriptional regulation of anthocyanin biosynthesis in B. napus and provide valuable genetic resources for breeding B. napus varieties with novel flower colors.

Abstract Background This retrospective study aimed to evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in Chinese patients with primary congenital glaucoma (PCG) and identify factors influencing surgical success. Methods Fourteen patients (24 eyes) diagnosed with PCG who underwent gonioscopy-assisted transluminal trabeculotomy were recruited, and data on intraocular pressure (IOP), antiglaucoma medication, surgery-related complications, and additional treatments were collected during preoperative and postoperative visits. Surgical success was defined as IOP ≤ 21 mmHg and a reduction of > 30% from baseline, with (partial success) or without (complete success) antiglaucoma medication. Results Mean preoperative IOP was 30.41 ± 6.09 mmHg. At the final visit, mean IOP reduction was 16.1 ± 9.1 mmHg (52%), and 19 of 24 eyes were topical medication–free. IOP was significantly decreased at each postoperative visit compared with baseline (P

Abstract Background Meningitic Escherichia coli (E. coli) is the major etiological agent of bacterial meningitis, a life-threatening infectious disease with severe neurological sequelae and high mortality. The major cause of central nervous system (CNS) damage and sequelae is the bacterial-induced inflammatory storm, where the immune response of the blood-brain barrier (BBB) is crucial. Methods Western blot, real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and dual-luciferase reporter assay were used to investigate the suppressor role of transforming growth factor beta 1 (TGFβ1) in the immune response of brain microvascular endothelial cells elicited by meningitic E. coli. Result In this work, we showed that exogenous TGFβ1 and induced noncanonical Hedgehog (HH) signaling suppressed the endothelial immune response to meningitic E. coli infection via upregulation of intracellular miR-155. Consequently, the increased miR-155 suppressed ERK1/2 activation by negatively regulating KRAS, thereby decreasing IL-6, MIP-2, and E-selectin expression. In addition, the exogenous HH signaling agonist SAG demonstrated promising protection against meningitic E. coli-induced neuroinflammation. Conclusion Our work revealed the effect of TGFβ1 antagonism on E. coli-induced BBB immune response and suggested that activation of HH signaling may be a potential protective strategy for future bacterial meningitis therapy. Video Abstract

Abstract Background MYB transcription factors are splay a vital role in plant biology, with previous research highlighting the significant impact of the R2R3-MYB-like transcription factor MYB5 on seed mucilage biosynthesis, trichome branching, and seed coat development. However, there is a dearth of studies investigating its role in the regulation of proanthocyanidin (PA) biosynthesis. Results In this study, a total of 51 MYB5 homologous genes were identified across 31 species belonging to the Brassicaceae family, with particular emphasis on Brassica napus for subsequent investigation. Through phylogenetic analysis, these genes were categorized into four distinct subclasses. Protein sequence similarity and identity analysis demonstrated a high degree of conservation of MYB5 among species within the Brassicaceae family. Additionally, the examination of selection pressure revealed that MYB5 predominantly underwent purifying selection during its evolutionary history, as indicated by the Ka/Ks values of all MYB5 homologous gene pairs being less than one. Notably, we observed a higher rate of non-synonymous mutations in orthologous genes compared to paralogous genes, and the Ka/Ks value displayed a stronger correlation with Ka. In B. napus, an examination of expression patterns in five tissues revealed that MYB5 exhibited particularly high expression in the black seed coat. The findings from the WGCNA demonstrated a robust correlation between MYB5 and BAN(ANR) associated with PA biosynthesis in the black seed coat, providing further evidence of their close association and co-expression. Furthermore, the results obtained from of the analysis of protein interaction networks offer supplementary support for the proposition that MYB5 possesses the capability to interact with transcriptional regulatory proteins, specifically TT8 and TT2, alongside catalytic enzymes implicated in the synthesis of PAs, thereby making a contribution to the biosynthesis of PAs. These findings imply a plausible and significant correlation between the nuique expression pattern of MYB5 and the pigmentation of rapeseed coats. Nevertheless, additional research endeavors are imperative to authenticate and substantiate these findings. Conclusions This study offers valuable insights into the genetic evolution of Brassicaceae plants, thereby serving as a significant reference for the genetic enhancement of Brassicaceae seed coat color.

Abstract Bacterial meningitis remains a leading cause of infection-related mortality worldwide. Although Escherichia coli (E. coli) is the most common etiology of neonatal meningitis, the underlying mechanisms governing bacterial blood-brain barrier (BBB) disruption during infection remain elusive. We observed that infection of human brain microvascular endothelial cells with meningitic E. coli triggers the activation of early growth response 1 (Egr-1), a host transcriptional activator. Through integrated chromatin immunoprecipitation sequencing and transcriptome analysis, we identified Egr-1 as a crucial regulator for maintaining BBB integrity. Mechanistically, Egr-1 induced cytoskeletal changes and downregulated tight junction protein expression by directly targeting VEGFA, PDGFB, and ANGPTL4, resulting in increased BBB permeability. Meanwhile, Egr-1 also served as a master regulator in the initiation of neuroinflammatory response during meningitic E. coli infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic E. coli, highlighting a promising therapeutic target for bacterial meningitis.

Abstract Air gap impulse discharge characteristics of railway tunnel‐catenary at high‐altitude are of great significance to the electrical insulation design. The existing altitude correction methods for non‐uniform air gaps are not applicable to tunnel‐catenary. To investigate the impulse discharge characteristics of the tunnel‐catenary, a typical structural model was built in an artificial climate chamber. Different altitudes were simulated by adjusting the atmospheric pressure. The 50% breakdown voltages of the 300–700 mm tunnel‐catenary gap were tested at 243–4000 m. The test found that the altitude/atmospheric pressure and gap length have an evident effect on the 50% impulse breakdown voltage, and the influence of humidity is relatively small. The polarity effect was analysed by streamer theory. The {d, P, h} parameter method was employed to obtain the fitting formulas for the impulse breakdown voltage. A high‐altitude correction method for the tunnel‐catenary breakdown voltage based on 1 km altitude was proposed. Field natural tests were conducted to verify the accuracy of the proposed method. The results show that the breakdown voltage obtained by the correction method has an average error of 3.66% in the results of the field tests, indicating that the method has engineering application prospects.

With the advancement of pacing technologies, His-Purkinje conduction system pacing (HPCSP) has been increasingly recognized as superior to conventional right ventricular pacing (RVP) and biventricular pacing (BVP). This method is characterized by a series of strategies that either strengthen the native cardiac conduction system or fully preserve physical atrioventricular activation, ensuring optimal clinical outcomes. Treatment with HPCSP is divided into two pacing categories, His bundle pacing (HBP) and left bundle branch pacing (LBBP), and when combined with atrioventricular node ablation (AVNA), can significantly improve left ventricular (LV) function. It effectively prevents tachycardia and regulates ventricular rates, demonstrating its efficacy and safety across different QRS wave complex durations. Therefore, HPCSP combined with AVNA can alleviate symptoms and improve the quality of life in patients with persistent atrial fibrillation (AF) who are unresponsive to multiple radiofrequency ablation, particularly those with concomitant heart failure (HF) who are at risk of further deterioration. As a result, this “pace and ablate” strategy could become a first-line treatment for refractory AF. As a pacing modality, HBP faces challenges in achieving precise localization and tends to increase the pacing threshold. Thus, LBBP has emerged as a novel approach within HPCSP, offering lower thresholds, higher sensing amplitudes, and improved success rates, potentially making it a preferable alternative to HBP. Future large-scale, prospective, and randomized controlled studies are needed to evaluate patient selection and implantation technology, aiming to clarify the differential clinical outcomes between pacing modalities.