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Using a biopsychosocial framework, our study examines the biological, psychological, and sociocultural factors associated with depression among a cross-sectional sample of undergraduate international students (N = 712) attending 28 U.S. colleges and universities. Consistent with hypotheses, regression analysis reveals that self-esteem, life satisfaction, and coping self-efficacy are negatively associated with depressive symptoms, and that ethnic minority status, perceived discrimination, and financial concerns are positively associated with depressive symptoms. Contrary to predictions, age, optimism, friendships, and school belonging are not significant predictors, and perseverance predicted increases depression in this sample. The novel findings highlight adaptation issues among international undergraduate students and suggest preventive measures and interventions against depression for university administrators and counselors.

Special education teacher (SET) burnout is a significant concern, especially for SETs serving students with emotional-behavioral disorders (EBD), as they tend to experience higher burnout than other teachers. Working conditions, especially social support, have the potential to ameliorate burnout, but prior research has not articulated the sources and types of social support that are most important. The authors conducted a longitudinal study, surveying 230 SETs serving students with EBD at three time points across one school year. Data revealed administrative support, adequacy of planning time, and autonomy in fall predicted emotional exhaustion and personal accomplishment in winter and spring. Associations between working conditions and burnout components were partially mediated by SETs' perceptions of workload manageability. SET change in well-being due to COVID-19 during the early months of the pandemic was not associated with burnout. The authors discuss implications, limitations, and directions for future inquiry.

We examined changes in burnout across three timepoints in one school year, in a sample (N = 230) of special educators serving students with emotional-behavioral disorders, in 15 school districts selected through stratified random sampling at the national level. Emotional exhaustion decreased at each timepoint in the school year and personal accomplishment increased from fall to spring. Latent growth curve modeling did not produce latent trajectories of burnout among teachers; however, cross-lagged panel structure equation modeling revealed that emotional exhaustion and personal accomplishment had both direct and indirect effects on depersonalization. Differences in burnout were significant by race/ethnicity but not by gender. Participants reported higher emotional exhaustion, lower depersonalization, and higher personal accomplishment than a national sample. We provide implications for researchers and practitioners.

Purpose: Previous studies highlight paraspinal muscles' significance in spinal stability. This study aims to assess paraspinal muscle predictiveness for postoperative recurrent lumbar disc herniation (PRLDH) after lumbar disc herniation patients undergo percutaneous endoscopic transforaminal discectomy (PETD). Patients and Methods: Retrospectively collected data from 232 patients undergoing PETD treatment at our institution between January 2020 and January 2023, randomly allocated into training (60%) and validation (40%) groups. Utilizing Lasso regression and multivariable logistic regression, independent risk factors were identified in the training set to construct a Nomogram model. Internal validation employed Enhanced Bootstrap, with Area Under the ROC Curve (AUC) assessing accuracy. Calibration was evaluated through calibration curves and the Hosmer-Lemeshow goodness-of-fit test. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed for clinical utility analysis. Results: Diabetes, Modic changes, and ipsilesional multifidus muscle skeletal muscle index (SMI) were independent predictive factors for PRLDH following PETD (P< 0.05). Developed Nomogram model based on selected predictors, uploaded to a web page. AUC for training: 0.921 (95% CI 0.872– 0.970), validation: 0.900 (95% CI 0.828– 0.972), respectively. The Hosmer-Lemeshow test yielded χ2=5.638/6.259, P=0.688/0.618, and calibration curves exhibited good fit between observed and predicted values. DCA and CIC demonstrate clinical net benefit for both models at risk thresholds of 0.02– 1.00 and 0.02– 0.80. Conclusion: The Nomogram predictive model developed based on paraspinal muscle parameters in this study demonstrates excellent predictive capability and aids in personalized risk assessment for PRLDH following PETD. [ABSTRACT FROM AUTHOR]

β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3ʹ splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted β654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the β-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from β654-ER mice on β-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future. [ABSTRACT FROM AUTHOR]

Background: LentiGlobin BB305 is a self‐inactivating lentiviral vector carrying a human β‐globin expressing cassette for treating β‐thalassemia. Initially, a 2 × 250 bp chicken Locus Control Region fragment of cHS4, functioning as an insulator, was placed at its ΔU3, which was removed after the first clinical trial led by a French team to avoid abnormal splicing, etc. This action could potentially lead to an increasing risk of the transcriptional read‐through rate driven by the β‐globin promoter to a significant level, posing a biosafety risk in clinical trials. Methods: In the present study, a read‐through reducing agent (C‐U+ or WPRE) was designed to be placed at the 3′ UTR of the β‐globin gene. The Enhancer Activities and/or Transcriptional Read‐Through (EATRT) rate at the mRNA level and the protein expression level regarding lentiviral preparation titer were examined. Results: We found that the insertion of the element (C‐U+ or WPRE) reduced the EATRT effectively by 53% or 41%, respectively. C‐U+ has less impact on virus package efficiency. Furthermore, there was no significant difference in the protein expression level after the C‐U+ or WPRE insertion. Conclusions: The results of the present study show that inserting C‐U+ or WPRE before the polyA sequence of the BB305 would reduce the EATRT rate at no cost of its expressing efficacy and viral preparation titers. Thus, we present an alternative improvement for a safer lentiviral vector for β‐thalassemia clinical trials. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) are stem cells that can differentiate into various blood cells and have long-term self-renewal capacity. At present, HSC transplantation is an effective therapeutic means for many malignant hematological diseases, such as aplastic hematological diseases and autoimmune diseases. The hematopoietic microenvironment affects the proliferation, differentiation, and homeostasis of HSCs. The regulatory effect of the hematopoietic microenvironment on HSCs is complex and has not been thoroughly studied yet. In this study, we focused on mononuclear cells (MNCs), which provided an important microenvironment for HSCs and established a methodological system for identifying cellular composition by means of multiple technologies and methods. First, single-cell RNA sequencing (scRNA-seq) technology was used to investigate the cellular composition of cells originating from different microenvironments during different stages of hematopoiesis, including mouse fetal liver mononuclear cells (FL-MNCs), bone marrow mononuclear cells (BM-MNCs), and in vitro-cultured fetal liver stromal cells. Second, bioinformatics analysis showed a higher proportion and stronger proliferation of the HSCs in FL-MNCs than those in BM-MNCs. On the other hand, macrophages in in vitro-cultured fetal liver stromal cells were enriched to about 76%. Differential gene expression analysis and Gene Ontology (GO) functional enrichment analysis demonstrated that fetal liver macrophages have strong cell migration and actin skeleton formation capabilities, allowing them to participate in the hematopoietic homeostasis through endocytosis and exocytosis. Last, various validation experiments such as quantitative real-time PCR (qRT-PCR), ELISA, and confocal image assays were performed on randomly selected target genes or proteins secreted by fetal liver macrophages to further demonstrate the potential relationship between HSCs and the cells inhabiting their microenvironment. This system, which integrates multiple methods, could be used to better understand the fate of these specific cells by determining regulation mechanism of both HSCs and macrophages and could also be extended to studies in other cellular models. [ABSTRACT FROM AUTHOR]

Limb‐girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium‐dependent neutral cysteine protease calpain‐3 (CAPN3). In our study, the compound heterozygosity with two missense variants c.635 T > C (p.Leu212Pro) and c.2120A > G (p.Asp707Gly) was identified in patients with LGMDR1. However, the pathogenicity of c.635 T > C has not been investigated. To evaluate the effects of this novel likely pathogenic variant to the motor system, the mouse model with c.635 T > C variant was prepared by CRISPR/Cas9 gene editing technique. The pathological results revealed that a limited number of inflammatory cells infiltrated the endomyocytes of certain c.635 T > C homozygous mice at 10 months of age. Compared with wild‐type mice, motor function was not significantly impaired in Capn3 c. 635 T > C homozygous mice. Western blot and immunofluorescence assays further indicated that the expression levels of the Capn3 protein in muscle tissues of homozygous mice were similar to those of wild‐type mice. However, the arrangement and ultrastructural alterations of the mitochondria in the muscular tissues of homozygous mice were confirmed by electron microscopy. Subsequently, muscle regeneration of LGMDR1 was simulated using cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. The repair of the homozygous mice was significantly worse than that of the control mice at day 15 and day 21 following treatment, the c.635 T > C variant of Capn3 exhibited a significant effect on muscle regeneration of homozygous mice and induced mitochondrial damage. RNA‐sequencing results demonstrated that the expression levels of the mitochondrial‐related functional genes were significantly downregulated in the mutant mice. Taken together, the results of the present study strongly suggested that the LGMDR1 mouse model with a novel c.635 T > C variant in the Capn3 gene was significantly dysfunctional in muscle injury repair via impairment of the mitochondrial function. [ABSTRACT FROM AUTHOR]

Conventional silicon (Si)-based power devices face physical limitations—such as switching speed and energy efficiency—which can make it difficult to meet the increasing demand for high-power, low-loss, and fast-switching-frequency power devices in power electronic converter systems. Gallium nitride (GaN) is an excellent candidate for next-generation power devices, capable of improving the conversion efficiency of power systems owing to its wide band gap, high mobility, and high electric breakdown field. Apart from their cost effectiveness, GaN-based power high-electron-mobility transistors (HEMTs) on Si substrates exhibit excellent properties—such as low ON-resistance and fast switching—and are used primarily in power electronic applications in the fields of consumer electronics, new energy vehicles, and rail transit, amongst others. During the past decade, GaN-on-Si power HEMTs have made major breakthroughs in the development of GaN-based materials and device fabrication. However, the fabrication of GaN-based HEMTs on Si substrates faces various problems—for example, large lattice and thermal mismatches, as well as 'melt-back etching' at high temperatures between GaN and Si, and buffer/surface trapping induced leakage current and current collapse. These problems can lead to difficulties in both material growth and device fabrication. In this review, we focused on the current status and progress of GaN-on-Si power HEMTs in terms of both materials and devices. For the materials, we discuss the epitaxial growth of both a complete multilayer HEMT structure, and each functional layer of a HEMT structure on a Si substrate. For the devices, breakthroughs in critical fabrication technology and the related performances of GaN-based power HEMTs are discussed, and the latest development in GaN-based HEMTs are summarised. Based on recent progress, we speculate on the prospects for further development of GaN-based power HEMTs on Si. This review provides a comprehensive understanding of GaN-based HEMTs on Si, aiming to highlight its development in the fields of microelectronics and integrated circuit technology. [ABSTRACT FROM AUTHOR]

A novel E-mode gallium nitride (GaN) high-electron-mobility field-effect transistor (HEMT) was prepared by combining a superlattice barrier with Mg by thermal diffusion doping. The new device can effectively overcome the disadvantages of the conventional p-GaN gate E-mode HEMT process, which include high etching accuracy requirements, difficult p-type doping, weak gate control, and large gate leakage. The device obtained in this study has a threshold voltage of 1.17 V, an output current of 227 mA mm−1 at VG = 3 V, a gate leakage of 2.0 × 10−8 mA mm−1 at VG = 0 V, and a breakdown voltage of up to 405 V. The high-voltage, low-gate-leakage current power device developed in this work could be used as a new type of E-mode power device. [ABSTRACT FROM AUTHOR]

Special education teacher (SET) burnout is a significant concern, especially for SETs serving students with emotional–behavioral disorders (EBD), as they tend to experience higher burnout than other teachers. Working conditions, especially social support, have the potential to ameliorate burnout, but prior research has not articulated the sources and types of social support that are most important. The authors conducted a longitudinal study, surveying 230 SETs serving students with EBD at three time points across one school year. Data revealed administrative support, adequacy of planning time, and autonomy in fall predicted emotional exhaustion and personal accomplishment in winter and spring. Associations between working conditions and burnout components were partially mediated by SETs' perceptions of workload manageability. SET change in well-being due to COVID-19 during the early months of the pandemic was not associated with burnout. The authors discuss implications, limitations, and directions for future inquiry. [ABSTRACT FROM AUTHOR]

Objectives: Mesoderm, derived from a new layer between epiblast and hypoblast during gastrulation, can differentiate into various tissues, including muscles, bones, kidneys, blood, and the urogenital system. However, systematic elucidation of mesoderm characteristics and specific markers remains a challenge. This study aims to screen and identify candidate genes important for mesoderm development. Materials and Methods: Cells originating from the three germ layers were obtained by laser capture microdissection, followed by microcellular RNA sequencing. Mesoderm‐specific differentially expressed genes (DEGs) were identified by using a combination of three bioinformatics pipelines. Candidate mesoderm‐specific genes expression were verified by real‐time quantitative polymerase chain reaction analysis and immunohistochemistry. Functional analyses were verified by ESCs‐EBs differentiation and colony‐forming units (CFUs) assay. Results: A total of 1962 differentially expressed mesoderm genes were found, out of which 50 were candidate mesoderm‐specific DEGs which mainly participate in somite development, formation of the primary germ layer, segmentation, mesoderm development, and pattern specification process by GO analysis. Representative genes Cdh2, Cdh11, Jag1, T, Fn‐1, and Pcdh7 were specifically expressed in mesoderm among the three germ layers. Pcdh7 as membrane‐associated gene has hematopoietic‐relevant functions identified by ESCs‐EBs differentiation and CFUs assay. Conclusions: Spatial transcriptomic profiling with multi‐method analysis and confirmation revealed candidate mesoderm progenitors. This approach appears to be efficient and reliable and can be extended to screen and validate candidate genes in various cellular systems. [ABSTRACT FROM AUTHOR]

Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome cause a group of genetic diseases termed ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). In the current study, a de novo c.352C>T (p.Gln118*) mutation in ZC4H2 (NM_018684.4) was identified in a female neonate born with severe arthrogryposis multiplex congenita (AMC) and Pierre-Robin sequence (cleft palate and micrognathia). Plasmids containing the wild-type (WT), mutant-type (MT) ZC4H2, or GFP report gene (N) were transfected in 293T cell lines, respectively. RT-qPCR and western blot analysis showed that ZC4H2 protein could not be detected in the 293T cells transfected with MT ZC4H2. The RNA seq results revealed that the expression profile of the MT group was similar to that of the N group but differed significantly from the WT group, indicating that the c.352C>T mutation resulted in the loss of function of ZC4H2. Differentially expressed genes (DEGs) enrichment analysis showed that c.352C>T mutation inhibited the expression levels of a series of genes involved in the oxidative phosphorylation pathway. Subsequently, expression levels of ZC4H2 were knocked down in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed small hairpin RNAs (shRNAs) against ZC4H2. The results also demonstrated that decreasing the expression of ZC4H2 significantly reduced the growth of NSCs by affecting the expression of genes related to the oxidative phosphorylation signaling pathway. Taken together, our results strongly suggest that ZC4H2 c.352C>T (p.Gln118*) mutation resulted in the loss of protein function and caused WRWFFR. [ABSTRACT FROM AUTHOR]

Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem [...]

Pantothenate kinase associated neurodegeneration (PKAN) is a severe autosomal recessive rare disease and characterized by iron accumulation in the basal ganglia. To investigate the pathogenesis of this disease in two sibling patients with PANK in a Chinese family, whole-exome variant detection and functional analysis were performed. Clinical and radiographic investigations were performed in the two brother patients. Whole exome sequencing (WES) was used in mutation detection, and the mutations were confirmed by Sanger sequencing. A longevity cohort genetic database was applied as Chinese urban controls. Bioinformatic analysis was performed to predict the pathogenicity. Compound heterozygous mutations of PANK2 were detected in two sibling brothers with PKAN in a Chinese family: c.510_522del (p.A170fs) and c.1319G > C (p.R440P) in the transcript NM_153638. PANK2: c.510_522del (p.A170fs) was absent in public data and the Chinese urban controls. Bioinformatics analysis showed that the above two variants were pathogenicity. We identified a rare compound heterozygous combination of PANK2 mutations found in a Chinese family in which two sibling brothers suffered from PKAN. PANK2 c.510_522del (p.A170fs) was the first reported to be a PKAN pathogenic variant. [ABSTRACT FROM AUTHOR]

Objectives: Early embryo development is dependent on the regulation of maternal messages stored in the oocytes during the maternal‐to‐zygote transition. Previous studies reported variability of oocyte competence among different inbred mouse strains. The present study aimed to identify the maternal transcripts responsible for early embryonic development by comparing transcriptomes from oocytes of high‐ or low‐ competence mouse strains. Materials and Methods: In vitro fertilization embryos from oocytes of different mouse strains were subject to analysis using microarrays, RNA sequencing, real‐time quantitative PCR (RT‐qPCR) analysis, Western blotting, and immunofluorescence. One candidate gene, Prkce, was analysed using Prkce knockout mice, followed by a cRNA rescue experiment. Results: The fertilization and 2‐cell rate were significantly higher for FVB/NJ (85.1% and 82.0%) and DBA/2J (79.6% and 76.7%) inbred mouse strains than those for the MRL/lpr (39.9% and 35.8%) and 129S3 (35.9% and 36.6%) strains. Thirty‐nine differentially expressed genes (DEGs) were noted, of which nine were further verified by RT‐qPCR. Prkce knockout mice showed a reduced 2‐cell rate (Prkce+/+ 80.1% vs. Prkce−/− 32.4%) that could be rescued by Prkce cRNA injection (2‐cell rate reached 76.7%). Global transcriptional analysis revealed 143 DEGs in the knockout mice, which were largely composed of genes functioning in cell cycle regulation. Conclusions: The transcription level of maternal messages such as Prkce in mature oocytes is associated with different 2‐cell rates in select inbred mouse strains. Prkce transcript levels could serve as a potential biomarker to characterize high‐quality mature oocytes. [ABSTRACT FROM AUTHOR]

The surface of carp is easily damaged during the descaling process, which jeopardizes the quality and safety of carp products. Damage recognition realized by manual detection is an important factor restricting the automation in the pretreatment. For the commonly used methods of mechanical and water‐jet descaling, damage area recognition according to the hyperspectral data was proposed. Two discrimination models, including decision tree (DT) and self‐organizing feature mapping (SOM), were established to recognize the damaged and normal descaling area with the average spectral value. The damage‐discrimination model based on DT was determined to be the optimal one, which possessed the best model performance (accuracy = 96.7%, sensitivity = 96.7%, specificity = 96.7%, F1‐score = 96.7%). Considering the efficiency and precision of damage‐area recognition and visualization, the principal component analysis (PCA) combined with pixel values statistical analysis was used to reduce the dimension of hyperspectral images at the image level. Through statistical analysis, the value 0 was used as the threshold to distinguish the normal area and the damaged area in the PC image to achieve preliminary segmentation. Then, the spectral values of the initially discriminated damage area were input into the DT discrimination model to realize the final discriminant of damaged area. On this basis, the position information of the damaged area could be used to realize the visualization. The final visualization maps for mechanical and water‐jet descaling damage were obtained by image morphology processing. The average recognition accuracy can reach 94.9% and 90.3%, respectively. The results revealed that the hyperspectral imaging technique has great potential to recognize the carp damage area nondestructively and accurately under descaling processing. Practical Application: This study demonstrated that hyperspectral imaging technique can realize the carp damage area detection nondestructively and accurately under descaling processing. With the advantages of nondestructive and rapid, hyperspectral imaging system and the method can be widely expanded and applied to the quality detection of other freshwater fish pretreatment. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.08.015 Byline: Paula Stein, Fanyi Zeng, Hua Pan, Richard M. Schultz Keywords: RNAi; dsRNA; Oocyte; Interferon response; Off-targeting Abstract: RNA interference (RNAi) is a conserved eukaryotic mechanism by which double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNAs. Recent concerns have arisen in mammalian systems about off-target effects of RNAi, as well as an interferon response. Most mammalian cells respond to long dsRNAs by inducing an antiviral response mediated by interferon that leads to general inhibition of protein synthesis and nonspecific degradation of mRNAs. Moreover, recent reports demonstrate that under certain conditions, short interfering RNAs (siRNAs, 21-25 bp) may activate the interferon system. Mouse oocytes and preimplantation embryos apparently lack this response, as potent and specific inhibition of gene expression triggered by long dsRNA is observed in these cells. In the present study, we analyzed the global pattern of gene expression by microarray analysis in transgenic mouse oocytes expressing long dsRNA and find no evidence of off-targeting. We also report that genes involved in the interferon response pathway are not expressed in mouse oocytes, even after exposure for an extended period of time to long dsRNA. Author Affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104-6018, USA Article History: Received 12 July 2005; Revised 11 August 2005; Accepted 12 August 2005

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.03.038 Byline: Fanyi Zeng, Richard M. Schultz Keywords: Microarray; Gene expression; Zygotic gene activation; Preimplantation mouse embryo Abstract: Zygotic gene activation is essential for development beyond the 2-cell stage in the preimplantation mouse embryo. Based on [alpha]-amanitin-sensitive BrUTP incorporation, transcription initiates in the 1-cell embryo and a major reprogramming of gene expression driven by newly expressed genes is prominently observed during the 2-cell stage. Superimposed on genome activation is the development of a transcriptionally repressive state that is mediated at the level of chromatin structure. The identity of the genes that are expressed during the 1- and 2-cell stages, however, is poorly described, as are those genes involved in mediating the transcriptionally repressive state. Using the Affymetrix MOE430 mouse GeneChip set, we characterized the set of [alpha]-amanitin-sensitive genes expressed during the 1- and 2-cell stages, and we used Expression Analysis Systematic Explorer (EASE) and Ingenuity Pathway Analysis (IPA) to identify biological and molecular processes represented by these genes, as well as interactions among them. We find that although the 1-cell embryo is transcriptionally active, we did not detect any transcripts present on the MOE430 GeneChip set to be [alpha]-amanitin-sensitive. Thus, what the BrUTP incorporation represents remains elusive. About 17% of genes expressed in the 2-cell embryo are [alpha]-amanitin-sensitive. EASE analysis reveals that genes involved in ribosome biogenesis and assembly, protein synthesis, RNA metabolism and transcription are over-represented, suggesting that genome activation during 2-cell stage may not be as global and promiscuous as previously proposed. IPA implicated Myc and Hdac1 as candidate genes involved in genome activation and the development of the transcriptionally repressive state, respectively. Author Affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104-6018, USA Article History: Received 4 January 2005; Revised 28 March 2005; Accepted 29 March 2005

Studies using low-resolution methods to assess gene expression during preimplantation mouse development indicate that changes in gene expression either precede or occur concomitantly with the major morphological transitions, that is, conversion of the oocyte to totipotent 2-cell blastomeres, compaction, and blastocyst formation. Using microarrays, we characterized global changes in gene expression and used Expression Analysis Systematic Explorer (EASE) to identify biological and molecular processes that accompany and likely underlie these transitions. The analysis confirmed previously described processes or events, but more important, EASE revealed new insights. Response to DNA damage and DNA repair genes are overrepresented in the oocyte compared to 1-cell through blastocyst stages and may reflect the oocyte's response to selective pressures to insure genomic integrity; fertilization results in changes in the transcript profile in the 1-cell embryo that are far greater than previously recognized; and genome activation during 2-cell stage may not be as global and promiscuous as previously proposed, but rather far more selective, with genes involved in transcription and RNA processing being preferentially expressed. These results validate this hypothesis-generating approach by identifying genes involved in critical biological processes that can be the subject of a more traditional hypothesis-driven approach. Keywords: Microarray; Gene expression; Genome activation; Maternal mRNA; Compaction; Blastocyst

RNA editing is a co- or post-transcriptional modification through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after transcription. Previous studies found that RNA editing may be critically involved in cancer and aging. However, the function of RNA editing in human early embryo development is still unclear. In this study, through analyzing single cell RNA sequencing data, 36.7% RNA editing sites were found to have a have differential editing ratio among early embryo developmental stages, and there was a great reprogramming of RNA editing rates at the 8-cell stage, at which most of the differentially edited RNA editing sites (99.2%) had a decreased RNA editing rate. In addition, RNA editing was more likely to occur on RNA splicing sites during human early embryo development. Furthermore, long non-coding RNA (lncRNA) editing sites were found more likely to be on RNA splicing sites (odds ratio = 2.19, P = 1.37×10−8), while mRNA editing sites were less likely (odds ratio = 0.22, P = 8.38×10−46). Besides, we found that the RNA editing rate on lncRNA had a significantly higher correlation coefficient with the percentage spliced index (PSI) of lncRNA exons (R = 0.75, P = 4.90×10−16), which indicated that RNA editing may regulate lncRNA splicing during human early embryo development. Finally, functional analysis revealed that those RNA editing-regulated lncRNAs were enriched in signal transduction, the regulation of transcript expression, and the transmembrane transport of mitochondrial calcium ion. Overall, our study might provide a new insight into the mechanism of RNA editing on lncRNAs in human developmental biology and common birth defects. Author summary: RNA editing is a process by which selected nucleotides on RNA molecules are changed post transcription of RNA. This results in changes RNA sequences that are different from the corresponding DNA sequence at modified positions. However, this slight difference has a great impact on various biological processes. In this manuscript, we investigated the function of RNA editing during human early embryo development. Through analyzing the sequencing data and computational biology, we found that RNA editing could regulate the alternative splicing of long-noncoding RNAs (lncRNAs) in human early embryo development. Here, lncRNAs are special kind of RNAs that do not translate into proteins, but have functions in the regulation of other genes. Alternative splicing is a process through which RNA molecules can be spliced into different transcripts after transcription. Thus, our results indicated that RNA editing could regulate the alternative splicing of lncRNAs and further affect the expression of downstream genes in human early embryo development. RNA editing could be the reason for the tremendous change of gene expression profile in human early embryo development which was found the previous researches. [ABSTRACT FROM AUTHOR]

As an innovative strategy, edge computing has been considered a viable option to address the limitations of cloud computing in supporting the Internet-of-Things applications. However, due to the instability of the network and the increase of the attack surfaces, the security in edge-assisted IoT needs to be better guaranteed. In this paper, we propose an intelligent intrusion detection mechanism, FedACNN, which completes the intrusion detection task by assisting the deep learning model CNN through the federated learning mechanism. In order to alleviate the communication delay limit of federal learning, we innovatively integrate the attention mechanism, and the FedACNN can achieve ideal accuracy with a 50% reduction of communication rounds. [ABSTRACT FROM AUTHOR]