The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways.

BACKGROUND: Endometrial receptivity (ER), a pivotal event for successful embryo implantation, refers to the capacity of endometrium to allow the adhesion of the trophectoderm of the blastocyst to endometrial cells. In this paper, we set to elucidate whether the peptides encoded by lncRNAs could influence trophoblast cells' adhesion to endometrial cells. METHODS: WGCNA construction and bioinformatics were used to find out the ER-related lncRNAs with coding potential. Protein analysis was done by immunoblotting and immunofluorescence (IF) microscopy. CCK-8 and Calcein-AM/PI double staining assays were employed to evaluate cell viability. The effect of the peptide on trophoblast spheroids' adhesion to endometrial cells was evaluated. The RNA sequencing (RNA-seq) analysis was applied to identify downstream molecular processes. RESULTS: lncRNA LINC00339 was found to be related to ER development and it had been predicted to have protein-coding potential. LINC00339 had high occupancy of ribosomes and was confirmed to encode a 49-aa peptide (named LINC00339-205-49aa). LINC00339-205-49aa could promote the attachment of JAR trophoblast spheroids to Ishikawa endometrial cells in vitro. LINC00339-205-49aa also upregulated the expression of E-cadherin in Ishikawa cells. Mechanistically, MAPK and PI3K-Akt signaling pathways were involved in the modulation of LINC00339-205-49aa, which were activated by LINC00339-205-49aa in Ishikawa cells. CONCLUSION: These data demonstrate that a previously uncharacterized peptide encoded by lncRNA LINC00339 has the ability to enhance JAR trophoblast spheroids' adhesion to Ishikawa endometrial cells, highlighting a new opportunity for the development of drugs to improve ER.

Brain Networks Modulation during Simple and Complex Gait: A "Mobile Brain/Body Imaging" Study.

Walking encompasses a complex interplay of neuromuscular coordination and cognitive processes. Disruptions in gait can impact personal independence and quality of life, especially among the elderly and neurodegenerative patients. While traditional biomechanical analyses and neuroimaging techniques have contributed to understanding gait control, they often lack the temporal resolution needed for rapid neural dynamics. This study employs a mobile brain/body imaging (MoBI) platform with high-density electroencephalography (hd-EEG) to explore event-related desynchronization and synchronization (ERD/ERS) during overground walking. Simultaneous to hdEEG, we recorded gait spatiotemporal parameters. Participants were asked to walk under usual walking and dual-task walking conditions. For data analysis, we extracted ERD/ERS in α, ß, and γ bands from 17 selected regions of interest encompassing not only the sensorimotor cerebral network but also the cognitive and affective networks. A correlation analysis was performed between gait parameters and ERD/ERS intensities in different networks in the different phases of gait. Results showed that ERD/ERS modulations across gait phases in the α and ß bands extended beyond the sensorimotor network, over the cognitive and limbic networks, and were more prominent in all networks during dual tasks with respect to usual walking. Correlation analyses showed that a stronger α ERS in the initial double-support phases correlates with shorter step length, emphasizing the role of attention in motor control. Additionally, ß ERD/ERS in affective and cognitive networks during dual-task walking correlated with dual-task gait performance, suggesting compensatory mechanisms in complex tasks. This study advances our understanding of neural dynamics during overground walking, emphasizing the multidimensional nature of gait control involving cognitive and affective networks.

5-Nitrobenzo[c][1, 2, 5]selenadiazole as therapeutic agents in the regulation of oxidative stress and inflammation induced by influenza A(H1N1)pdm09 in vitro and in vivo.

Currently, various problems are being faced in the treatment of influenza, so the development of new safe and effective drugs is crucial. Selenadiazole, an important component of selenium heterocyclic compounds, has received wide attention for its biological activity. This study aimed to verify the antiviral activity of 5-nitrobenzo[c][1,2,5]selenadiazole (SeD-3) in vivo and in vitro. The cell counting kit-8 assay and observation of cytopathic effect verified that SeD-3 could improve the survival of influenza A(H1N1)pdm09-infected Madin-Darby canine kidney cells. Polymerase chain reaction quantification and neuraminidase assay showed that SeD-3 could inhibit the proliferation of H1N1 virus. The time of addition assay demonstrated that SeD-3 may have a direct effect on virus particles and block some stages of H1N1 life cycle after virus adsorption. Cell cycle, JC-1, Annexin V, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling-4',6-diamidino-2-phenylindole (TUNEL-DAPI) assays showed that SeD-3 inhibited H1N1 infection-induced apoptosis. Cytokine detection demonstrated SeD-3 inhibited the production of proinflammatory factors after infection, including tumor necrosis factor-α (TNF-α), TNF-ß, interferon-γ, interleukin 12 (IL-12), and IL-17F. In vivo experiments suggested that the pathological damage in the lungs was significantly alleviated after treatment with SeD-3 by hematoxylin and eosin staining. The TUNEL assay of lung tissues indicated that SeD-3 inhibited DNA damage during H1N1 infection. Immunohistochemical assays were performed to further explore the mechanism that SeD-3 inhibited H1N1-induced apoptosis via reactive oxygen species-mediated MAPK, AKT, and P53 signaling pathways. In conclusion, SeD-3 may become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Recognition elements based on the molecular biological techniques for detecting pesticides in food: A review.

Excessive use of pesticides can cause contamination of the environment and agricultural products that are directly threatening human life and health. Therefore, in the process of food safety supervision, it is crucial to conduct sensitive and rapid detection of pesticide residues. The recognition element is the vital component of sensors and methods for fast testing pesticide residues in food. Improper recognition elements may lead to defects of testing methods, such as poor stability, low sensitivity, high economic costs, and waste of time. We can use the molecular biological technique to address these challenges as a good strategy for recognition element production and modification. Herein, we review the molecular biological methods of five specific recognition elements, including aptamers, genetic engineering antibodies, DNAzymes, genetically engineered enzymes, and whole-cell-based biosensors. In addition, the application of these identification elements combined with biosensor and immunoassay methods in actual detection was also discussed. The purpose of this review was to provide a valuable reference for further development of rapid detection methods for pesticide residues.

Genome-Wide Characterization and Expression Analysis of Transcription Factor Families in Desert Moss Syntrichia caninervis under Abiotic Stresses.

Transcription factor (TF) families play important roles in plant stress responses. S. caninervis is a new model moss for plant desiccation tolerance studies. Here, we report a high-confidence identification and characterization of 591 TFs representing 52 families that covered all chromosomes in S. caninervis. GO term and KEGG pathway analysis showed that TFs were involved in the regulation of transcription, DNA-templated, gene expression, binding activities, plant hormone signal transduction, and circadian rhythm. A number of TF promoter regions have a mixture of various hormones-related cis-regulatory elements. AP2/ERF, bHLH, MYB, and C2H2-zinc finger TFs were the overrepresented TF families in S. caninervis, and the detailed classification of each family is performed based on structural features. Transcriptome analysis revealed the transcript abundances of some ScAP2/ERF, bHLH, MYB, and C2H2 genes were accumulated in the treated S. caninervis under cold, dehydration, and rehydration stresses. The RT-qPCR results strongly agreed with RNA-seq analysis, indicating these TFs might play a key role in S. caninervis response to abiotic stress. Our comparative TF characterization and classification provide the foundations for functional investigations of the dominant TF genes involved in S. caninervis stress response, as well as excellent stress tolerance gene resources for plant stress resistance breeding.

Frequency-dependent modulation of neural oscillations across the gait cycle.

Balance and walking are fundamental to support common daily activities. Relatively accurate characterizations of normal and impaired gait features were attained at the kinematic and muscular levels. Conversely, the neural processes underlying gait dynamics still need to be elucidated. To shed light on gait-related modulations of neural activity, we collected high-density electroencephalography (hdEEG) signals and ankle acceleration data in young healthy participants during treadmill walking. We used the ankle acceleration data to segment each gait cycle in four phases: initial double support, right leg swing, final double support, left leg swing. Then, we processed hdEEG signals to extract neural oscillations in alpha, beta, and gamma bands, and examined event-related desynchronization/synchronization (ERD/ERS) across gait phases. Our results showed that ERD/ERS modulations for alpha, beta, and gamma bands were strongest in the primary sensorimotor cortex (M1), but were also found in premotor cortex, thalamus and cerebellum. We observed a modulation of neural oscillations across gait phases in M1 and cerebellum, and an interaction between frequency band and gait phase in premotor cortex and thalamus. Furthermore, an ERD/ERS lateralization effect was present in M1 for the alpha and beta bands, and in the cerebellum for the beta and gamma bands. Overall, our findings demonstrate that an electrophysiological source imaging approach based on hdEEG can be used to investigate dynamic neural processes of gait control. Future work on the development of mobile hdEEG-based brain-body imaging platforms may enable overground walking investigations, with potential applications in the study of gait disorders.

Duvira Antarctic polysaccharide inhibited H1N1 influenza virus-induced apoptosis through ROS mediated ERK and STAT-3 signaling pathway.

BACKGROUND: The H1N1 influenza virus causes acute respiratory tract infection, and its clinical symptoms are very similar to those of ordinary influenza. The disease develops rapidly. If the flu is not treated, complications such as pneumonia, respiratory failure, and multiple organ damage can occur, resulting in a high fatality rate. Influenza virus mutates rapidly. At present, there is no specific drug for H1N1, so it is an urgent need for clinical care to find new drugs to treat H1N1. MATERIALS AND METHODS: The polysaccharide derived from Durvillaea Antarctica green algae has a certain antiviral effect. In this study, the results of CCK-8, apoptosis cycle detection, JC-1 and Western blotting proved that Duvira Antarctic polysaccharide (DAPP) has the ability to inhibit H1N1 infection. RESULTS: CCK-8 test showed that the DAPP with concentration at 32 µg/mL had no toxicity to MDCK cells. In addition, DAPP reduced cell apoptosis by inhibiting the ERK signaling pathway. Meanwhile, DAPP could increase the expression of STAT3 and significantly inhibited proinflammatory cytokines. CONCLUSIONS: In summary, these results suggested that DAPP may be potential with the ability to resist the H1N1 influenza virus.

Radical Hydro-Fluorosulfonylation of Unactivated Alkenes and Alkynes.

Recently, radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which are highly in demand in various disciplines, particularly in chemical biology and drug discovery. Here, we report the first establishment of radical hydro-fluorosulfonylation of alkenes, which is enabled by using 1-fluorosulfonyl 2-aryl benzoimidazolium (FABI) as an effective redox-active radical precursor. This method provides a new and facile approach for the synthesis of aliphatic sulfonyl fluorides from unactivated alkenes, and can be further applied to the late-stage modifications of natural products and peptides, as well as ligation of drugs in combination with click chemistry. Remarkably, this system could enable the radical hydro-fluorosulfonylation of alkynes, affording valuable alkenylsulfonyl fluoride products with a rare, high Z-selectivity, which are normally less stable and more challenging to synthesize in comparison with the E-configured products.

The inhibition of enterovirus 71 induced apoptosis by Durvillaea antarctica through P53 and STAT1 signaling pathway.

The infection of enterovirus 71 (EV71) resulted in hand, foot, and mouth disease and may lead to severe nervous system damage and even fatalities. There are no effective drugs to treat the EV71 virus and it is crucial to find novel drugs against it. Polysaccharide isolated from Durvillaea antarctica green algae has an antiviral effect. In this study, D. antarctica polysaccharide (DAPP) inhibited the infection of EV71 was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), reverse transcription polymerase chain reaction, flow cytometry, and western blot. MTT assay showed that DAPP had no toxicity on Vero cells at the concentration 250 µg/ml. Furthermore, DAPP significantly reduced the RNA level of EV71 in a dose-dependent manner. Moreover, DAPP inhibited the Vero cells apoptosis induced by EV71 via the P53 signaling pathway. Meanwhile, the expression of signal transducer and activator of transcription 1 and mammalian target of rapamycin were increased and the proinflammatory cytokines were significantly inhibited by DAPP. Taken together, these results suggested that DAPP could be a potential pharmaceutical against the infection of EV71 virus.

Heat shock protein 70 as a supplementary receptor facilitates enterovirus 71 infections in vitro.

As one of the major causative agents of hand, foot and mouth disease (HFMD), enterovirus 71 (EV71) is a small, non-enveloped positive stranded RNA virus. Children suffering EV71 infection may cause severe symptoms including neurological complications, pulmonary edema and aseptic meningitis. EV71 is a neurotropic virus and it can cause the damage of nervous cells, cytokine storm and toxic substance. Identifying the factors that mediate viral binding or entry to host cells is important to uncover the mechanisms which viruses utilize to cause diseases in human body. Heat shock protein 70 (HSP70) is induced during virus infection and facilitates proper protein folding during viral propagation. The role that HSP70 plays during EV71 infection is still unclear. In this study, siRNA interference technique and transgenic technique were used to investigate the interaction between HSP70 and EV71 virus. The result demonstrated that the cell surface HSP70 is not essential for EV71 infection but helps the initial binding of virus to host cells and that multiple receptors are involved during EV71 infection. In addition, HSP70 was upregulated in human neuroblastoma cells (SK-N-SH) infected with EV71.

Delivery of Doxorubicin for Human Cervical Carcinoma Targeting Therapy by Folic Acid-Modified Selenium Nanoparticles.

Cancer-specific drug delivery represents an attractive approach to preventing undesirable side effects and increasing the accumulation of the drug in tumors. The surface modification of selenium nanoparticles (SeNPs) with targeting moieties thus represents an effective strategy for cancer therapy. In this study, SeNPs were modified with folic acid (FA), whose receptors were overexpressed on the surface of cancer cells, including human cervical carcinoma HeLa cells, to fabricate tumor-targeting delivery carrier FA-SeNPs nanoparticles. Then, the anticancer drug doxorubicin (DOX) was loaded onto the surface of the FA-SeNPs for improving the antitumor efficacy of DOX in human cervical carcinoma therapy. The chemical structure characterization of FA-Se@DOX showed that DOX was successfully loaded to the surface of FA-SeNPs to prepare FA-Se@DOX nanoparticles. FA-Se@DOX exhibited significant cellular uptake in human cervical carcinoma HeLa cells (folate receptor overexpressing cells) in comparison with lung cancer A549 cells (folate receptor deficiency cells), and entered HeLa cells mainly by the clathrin-mediated endocytosis pathway. Compared to free DOX or Se@DOX at the equivalent dose of DOX, FA-Se@DOX showed obvious activity to inhibit HeLa cells' proliferation and induce the apoptosis of HeLa cells. More importantly, FA-Se@DOX could specifically accumulate in the tumor site, which contributed to the significant antitumor efficacy of FA-Se@DOX in vivo. Taken together, FA-Se@DOX may be one novel promising drug candidate for human cervical carcinoma therapy.

Recombinant heat shock protein 78 enhances enterovirus 71 propagation in Vero cells and is induced in SK-N-SH cells during the infection.

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD), which mainly occurs in children. Children with EV71 infection can develop severe neurological diseases. Heat shock protein 78 (HSP78) facilitates proper protein folding during viral propagation and is induced during virus infection. Nevertheless, the role that HSP78 plays during EV71 infection is still unclear. In this study, recombinant HSP78 protein was expressed in a prokaryotic expression system and used for exploring the interaction between HSP78 and EV71 propagation. Detection using a mouse immune anti-HSP78 serum in ELISA and western blot demonstrated that the recombinant HSP78 antigen is highly immunogenic. Furthermore, the recombinant HSP78 protein was able to bind to EV71 VP1 and intensified the cytopathic effect and viral propagation during EV71 infection, while the immune serum had a counteractive effect. However, knockdown of the HSP78 gene in Vero cells before EV71 infection did not result in a reduced virus titer. In addition, HSP78 on the cell surface was upregulated in human neuroblastoma cells (SK-N-SH) infected with EV71.

The Seroprevalence of Some Pathogen Specific IgM in Children with Acute Respiratory Tract Infections in Guangzhou Region, 2011 - 2012.

BACKGROUND: Acute respiratory tract infections (ARTIs) are the leading cause of morbidity and death in children < 5 years worldwide. The aim of this study is to analyze the seroprevalence of nine pathogen specific IgMs in children with ARTIs with respect to gender, age, and seasonality in the Guangzhou region. METHODS: Serum samples were collected from 20160 children with ARTIs admitted to the Guangzhou Women and Children's Medical Center between 2011 and 2012. Serum-specific IgM antibodies to nine respiratory pathogens, Mycoplasma pneumonia (MP), Legionella pneumophila (LP), Coxiella burnetii (C. burnetii), Chlamydophila pneumonia (CP), adenovirus (ADV), respiratory syncytial virus (RSV), type A and type B influenza virus (IVA and IVB), and parainfluenza virus (PIV), were detected using immunofluorescence assay. RESULTS: The male-to-female ratio of all patients was 1.9:1. The median age was 3 years and 8 months with a significant difference in seropositivity to respiratory tract pathogens between children from different age groups. Seropositivity was detected in 43.53% of the children with the top three pathogens being MP (33.15%), RSV (10.27%), and ADV (6.63%), followed by IVB (2.63%), LP (2.25%), IVA (1.59%), PIV (1.57%), CP (0.27%), and C. burnetii (0.13%). The prevalence of single, double, and triple seropositivity was 70.20% (6160/8775), 25.22% (2213/8775), and 4.57% (401/8775), respectively. The total IgM seropositivity for any kind of pathogen in the nine kinds of pathogens peaked in winter (46.53%), while the nadir was observed in summer (41.97%). CONCLUSIONS: The top three seroprevalence of nine kinds of pathogen specific IgM was MP, followed by RSV and ADV. The epidemic pathogen specific IgM had a season-specific seropositivity distribution. Seroprevalence of the pathogen should be a focus of attention.

The Serum Value of NO and IL-17 were Increased in Children with Influenza A Viral Pneumonia.

BACKGROUND: Influenza A virus can cause severe respiratory infection in children and even result in immune system dysfunction. The aim of this study is to examine the clinical value of peripheral blood lymphocytes and serum nitric oxide (NO) and cytokines in children with influenza A viral pneumonia. METHODS: Thirty children hospitalized with confirmed influenza A viral pneumonia and 30 healthy controls were enrolled in this study. The blood samples were collected from all the children and anti-coagulated with EDTA. The peripheral blood lymphocyte subsets were analyzed by flow cytometry. Griess assay were performed to calculate serum NO and nitrite (NO2-) levels. The serum concentrations of IFN-γ and IL-17 were measured by ELISA. RESULTS: The serum levels of NO, NO2-, and IL-17 were significantly higher in children with influenza A viral pneumonia than controls (p < 0.01), while the level of IFN-γ had no significant difference (p = 0.515). Additionally, the patients had significantly lower percentages of peripheral blood CD3+, CD3+CD4+ T lymphocytes, and CD56+CD16+ natural killer (NK) cells than controls (p < 0.05), while CD3+CD8+ and CD4-CD8- (double negative, DN) T lymphocytes did not differ significantly (p > 0.05). Correlation analysis suggests that the serum NO level is positively correlated with IL-17 (p < 0.05). Conclusions: The increased levels of NO and IL-17 may be related to dysregulated lymphocytes' immune response in children with influenza A viral pneumonia. These abnormalities may be the main cause of inflammatory lung damage, and thus have significant prognostic value.

ROS scavenging enzyme-encoding genes play important roles in the desert moss Syntrichia caninervis response to extreme cold and desiccation stresses.

Abiotic stress is one of the major environmental constraints limiting plant growth. Syntrichia caninervis is one of the unique plant models that can cope with harsh environments. Reactive oxygen species (ROS) are a vital signaling molecule for protecting plants from oxidative stress, but research on ROS in S. caninervis is limited. Here, we identified 112 ROS genes in S. caninervis, including 40 GSTs, 51 PODs, 9 SODs, 6 CATs, 3 GPXs and 3 APXs families. GO and KEGG analyses showed that ROS genes are involved in responses to various stimuli and phenylpropanoid biosynthesis. ROS genes contain many stress-responsive and hormonal cis-elements in their promoter regions. More ROS genes were induced by cold stress than desiccation stress, and both conditions changed the transcript abundances of several ROS genes. CAT and POD, H2O2, MDA, and GSH were also induced under biotic stress, specifically CAT activity. The results indicated that the ScCAT genes and their activities could be strongly associated with the regulation of ROS production. This is the first systematic identification of ROS genes in S. caninervis and our findings contribute to further research into the roles of ScROS adjustment under abiotic stress while also providing excellent genetic resources for plant breeding.

Dissemination of clinical Escherichia coli strains harboring mcr-1, blaNDM-7 and siderophore-producing plasmids in a Chinese hospital.

BACKGROUND: Carbapenem-resistant E. coli (CREco) pose a significant public health threat due to their multidrug resistance. Colistin is often a last-resort treatment against CREco; however, the emergence of colistin resistance gene mcr-1 complicates treatment options. METHODS: Two E. coli strains (ECO20 and ECO21), recovered from hospitalized patients in distinct wards, exhibited resistance to carbapenems and colistin. Whole-genome sequencing and phenotypic characterization were employed to study resistance patterns, plasmid profiles, transferability of resistance and virulence genes, and siderophore production capabilities. Comparative genome analysis was used to investigate the genetic environment of mcr-1, blaNDM-7, and virulence clusters. RESULTS: Both E. coli strains exhibited thr presence of both mcr-1 and blaNDM-7 genes, showing high resistance to multiple antibiotics. Genomic analysis revealed the clonal transmission of these strains, possessing identical plasmid profiles (pMCR, pNDM, and pVir) associated with colistin resistance, carbapenem resistance, and virulence factors. Conjugation experiments confirmed the transferability of these plasmids, indicating their potential to disseminate resistance and virulence traits to other strains. Comparative genomic analyses unveiled the distribution of mcr-1 (IncX4-type) and blaNDM (IncX3-type) plasmids across diverse bacterial species, emphasizing their adaptability and threat. The novelty of pVir indicates its potential role in driving the evolution of highly adaptable and pathogenic strains. CONCLUSIONS: Our findings underscore the co-occurrence of mcr-1, blaNDM-7, and siderophore-producing plasmids in E. coli, which poses a significant concern for global health. This research is crucial to unravel the complex mechanisms governing plasmid transfer and recombination and to devise robust strategies to control their spread in healthcare settings.

Multi-Omics Approaches Provide New Insights into the Identification of Putative Fungal Effectors from Valsa mali.

Pathogenic fungi secrete numerous effectors into host cells to manipulate plants' defense mechanisms. Valsa mali, a necrotrophic fungus, severely impacts apple production in China due to the occurrence of Valsa canker. Here, we predicted 210 candidate effector protein (CEP)-encoding genes from V. mali. The transcriptome analysis revealed that 146 CEP-encoding genes were differentially expressed during the infection of the host, Malus sieversii. Proteome analysis showed that 27 CEPs were differentially regulated during the infection stages. Overall, 25 of the 146 differentially expressed CEP-encoding genes were randomly selected to be transiently expressed in Nicotiana benthamiana. Pathogenicity analysis showed that the transient expression of VM1G-05058 suppressed BAX-triggered cell death while the expression of VM1G-10148 and VM1G-00140 caused cell death in N. benthamiana. In conclusion, by using multi-omics analysis, we identified potential effector candidates for further evaluation in vivo. Our results will provide new insights into the investigation of virulent mechanisms of V. mali.

Selenomethionine Inhibited HADV-Induced Apoptosis Mediated by ROS through the JAK-STAT3 Signaling Pathway.

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.

Large-scale analysis of neural activity and connectivity from high-density electroencephalographic data.

INTRODUCTION: High-density electroencephalography (hdEEG) is a technique used for the characterization of the neural activity and connectivity in the human brain. The analysis of EEG data involves several steps, including signal pre-processing, head modelling, source localization and activity/connectivity quantification. Visual check of the analysis steps is often necessary, making the process time- and resource-consuming and, therefore, not feasible for large datasets. FINDINGS: Here we present the Noninvasive Electrophysiology Toolbox (NET), an open-source software for large-scale analysis of hdEEG data, running on the cross-platform MATLAB environment. NET combines all the tools required for a complete hdEEG analysis workflow, from raw signals to final measured values. By relying on reconstructed neural signals in the brain, NET can perform traditional analyses of time-locked neural responses, as well as more advanced functional connectivity and brain mapping analyses. The extracted quantitative neural data can be exported to provide broad compatibility with other software. CONCLUSIONS: NET is freely available (https://github.com/bind-group-kul/net) under the GNU public license for non-commercial use and open-source development, together with a graphical user interface (GUI) and a user tutorial. While NET can be used interactively with the GUI, it is primarily aimed at unsupervised automation to process large hdEEG datasets efficiently. Its implementation creates indeed a highly customizable program suitable for analysis automation and tight integration into existing workflows.

Enhancement of the Tumor Suppression Effect of High-dose Radiation by Low-dose Pre-radiation Through Inhibition of DNA Damage Repair and Increased Pyroptosis.

Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.