Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury.

Modulation of the heart's immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors (Irf7, Batf2, and Stat1). Single-cell chromatin accessibility studies revealed an enrichment of these TF motifs at IFN-EC signature genes. Expression of immune regulatory ligand genes by IFN-ECs suggests bidirectional signaling between IFN-ECs and macrophages in regenerative-stage hearts. Our data suggest that ECs may adopt immune regulatory signatures after cardiac injury to accompany the reparative response. The presence of these signatures in human HF and murine MI models suggests a potential role for EC-mediated immune regulation in responding to stress induced by acute injury in MI and chronic adverse remodeling in HF.

α-Glucan derivatives as selective blockers of aldolase A: Computer-aided structure optimization and the effects on HCC.

Aldolase A (ALDOA) promotes hepatocellular carcinoma (HCC) growth and is a potential therapeutic target. A previous study found an α-D-glucan (α-D-(1,6)-Glcp-α-D-(1,4)-Glcp, 10.0:1.0), named HDPS-4II, that could specifically inhibit ALDOA but its activity was not high enough. In this study, the derivatives of α-D-glucan binding to ALDOA were optimized using molecular docking, and its sulfated modification demonstrated the highest affinity with ALDOA among sulfated, carboxylated, and aminated derivatives. Sulfated HDPS-4II and dextrans with different molecular weights (1000 Da, 3000 Da, and 4000 Da) were prepared. Using MST assay, 3-O-sulfated HDPS-4II (SHDPS-4II) and 1000 Da dextran (SDextran1) showed higher affinities to ALDOA with Kd of 1.83 µM and 85.04 µM, respectively. Furthermore, SHDPS-4II and SDextran1 markedly inhibited the proliferation of HCC cells both in vitro and in vivo by blocking ALDOA. These results demonstrate that sulfated modification of α-D-glucans could enhance their affinities with ALDOA and anti-HCC effects.

Soil phosphorus availability mediates the effects of nitrogen addition on community- and species-level phosphorus-acquisition strategies in alpine grasslands.

Plants modulate their phosphorus (P) acquisition strategies (i.e., change in root morphology, exudate composition, and mycorrhizal symbiosis) to adapt to varying soil P availability. However, how community- and species-level P-acquisition strategies change in response to nitrogen (N) supply under different P levels remains unclear. To address this research gap, we conducted an 8-year fully factorial field experiment in an alpine grassland on the Qinghai-Tibet Plateau (QTP) combined with a 12-week glasshouse experiment with four treatments (N addition, P addition, combined N and P addition, and control). In the field experiment (community-level), when P availability was low, N addition increased the release of carboxylate from roots and led to a higher percentage of colonisation by arbuscular mycorrhizal fungi (AMF), along with decreased root length, specific root length (SRL), and total root length colonised by AMF. When P availability was higher, N addition resulted in an increase in the plant's demand for P, accompanied by an increase in root diameter and phosphatase activity. In the glasshouse experiment (species-level), the P-acquisition strategies of grasses and sedge in response to N addition alone mirrored those observed in the field, exhibiting a reduction in root length, SRL, and total root length colonised, but an increased percentage of AMF colonisation. Forbs responded to N addition alone with increased investment in all P-acquisition strategies, especially increased root biomass and length. P-acquisition strategies showed consistent changes among all species in response to combined N and P addition. Our results suggest that increased carboxylate release and AMF colonisation rate are common P-acquisition strategies of plants in alpine grasslands under N-induced P limitation. The main difference in P-acquisition strategies between forbs and grasses/sedges in response to N addition under low-P conditions was an increase in root biomass and length.

Traditional uses, phytochemistry, pharmacology, applications, and quality control of Gastrodia elata Blume: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (G. elata) has a long historical application in Asian countries and its tubers, seeds, and stalks are capable of being utilized for medicine, food, or health care products. AIM OF THE REVIEW: This study aimed to offer a systematic and up-to-date analysis of the current review of the G. elata research advances in traditional uses, phytochemistry, pharmacology, applications, and quality control, as well as a scientific reference for the development and utilization of this plant. MATERIALS AND METHODS: Electronic databases including PubMed, Web of Science, Google Scholar, ScienceDirect, SciFinder, and CNKI were used for the collection of publications on G. elata. The following keywords of G. elata were used truncated with other relevant topic terms, such as phenolic compounds, polysaccharides, glycosides, neuroprotection, learning and memory improvement effects, cardioprotection, applications, and quality control. RESULTS AND CONCLUSIONS: Approximately 134 chemical components mainly categorizing as phenolic compounds, polysaccharides, glycosides, organic acids, and sterols were reported from this plant. Moreover, preclinical studies indicated that G. elata performs several functions, including neuroprotection, learning and memory improvement effects, cardioprotection, vaso-modulatory effect, anti-depression, anti-cancer, and other effects. Currently, G. elata has been widely applied to clinics and foods. The available literature shows that the quality of G. elata might be affected by factors such as origin, fungus, and harvest time, which will have an impact on the drug efficacy. According to past research, G. elata is a potential medicinal and edible plant with several active components and pharmacological activity that has a high application value in medicine and the food business. Nevertheless, few studies have concentrated on characterization of polysaccharides structure and study of non-medicinal parts, implying that further comprehensive research on its polysaccharides structure and non-medicinal parts is critical for full utilization of resources of G. elata.

Nucleolus imaging based on naphthalimide derivatives.

Nucleolus was an important cellular organelle. The abnormal morphology and number of the nucleolus have been considered as diagnostic biomarkers for some human diseases. However, the imaging agent based on nucleolus was limited. In this manuscript, a series of nucleolar fluorescent probes based on naphthalimide derivatives (NI-1 âˆ¼ NI-5) had been designed and synthesized. NI-1 âˆ¼ NI-5 could penetrate cell membranes and nuclear membranes, achieve clear nucleolar staining in living cells. These results suggested that the presence of amino groups on the side chains of naphthalimide backbone could enhance the targeting to the cell nucleolus. In addition, the molecular docking results showed that NI-1 âˆ¼ NI-5 formed hydrogen bonds and hydrophobic interactions with RNA, and exhibited enhanced fluorescence upon binding with RNA. These results will provide favorable support for the diagnosis and treatment of nucleolus-related diseases in the future.

Enhanced photocarrier separation in Br substitution-induced [W(VI)O6-x] units for highly efficient photocatalytic nitrate reduction under alkaline conditions.

Photocatalytic nitrate (NO3-) reduction is considered a promising green and non-polluting technology to solve the nitrate pollution of groundwater and surface water. Herein, a novel Br-substituted Bi2WO6-x ultrathin nanosheets were prepared by a simple hydrothermal method in a strong acid environment containing sixteen alkyl three methyl bromide (CTAB). The catalytic system solves the problems of low carrier separation efficiency, poor performance under alkaline conditions, and a hard-to-activate N = O bond, achieving efficient NO3- removal under alkaline conditions along with high N2 selectivity. It was confirmed that Br-substituted Bi2WO6-x produced the [W(VI)O6-x] units with a strong electron-withdrawing property by changing the polarity of the O-W-O bond. As a result, the effective space charge separation caused by the change of the W valence state and the spontaneous fracture behavior of the N = O bond improved the carriers utilization efficiency and distinctly reduced the reaction energy consumption, synergistically achieving excellent performance.

A comprehensive evaluation of milk protein molecular weight distribution based on exclusion chromatography dataset.

Molecular weight is one of the main characteristic parameters of proteins, which is the basis for the functional properties of milk protein. This research aims at establishing molecular weight distribution pattern of milk protein based on exclusion chromatography. The method selected Na3PO4-Na2SO4 (0.1 M, pH 6.7) buffer as the mobile phase and detected at 220 nm by HPLC-UV. The protein molecular weight distributions were determined and compared for human milk, bovine milk, and infant formula. The proportion of macromolecular proteins is much higher in infant formula compared to human or bovine milk. The protein molecular weights of human and bovine milk are significantly different around 90, 20, 14, and 2 kDa. The results provide holistic compare of bovine milk, human milk, and infant formula through protein molecular distribution. The new evaluation indicators for protein will drive technological simulation of infant formula.

Pre-COVID resting-state brain activity in the fusiform gyrus prospectively predicts social anxiety alterations during the pandemic.

BACKGROUND: Social anxiety (SA) has been linked to the coronavirus disease 2019 (COVID-19) pandemic, but the neurobiopsychological mechanisms underlying this relationship remain unclear. This study aimed to elucidate the neurofunctional markers for COVID-induced SA development and the potential role of COVID-related posttraumatic stress symptoms (PTSS) in the brain-SA alterations link. METHODS: Before the COVID-19 pandemic (T1), 100 general college students underwent resting-state magnetic resonance imaging and behavioral tests. During the period of community-level outbreaks (T2), these students were re-contacted to undergo follow-up behavioral assessments. RESULTS: Whole-brain correlation and prediction analyses found that pre-pandemic spontaneous neural activity (measured by fractional amplitude of low-frequency fluctuations) in the right fusiform gyrus (FG) was positively correlated to SA alterations (T2 - T1). Mediation analyses revealed that COVID-specific PTSS mediated the effects of right FG on SA alterations. LIMITATIONS: The results should be interpreted carefully because only one-session neuroimaging data in a sample of normal adults were included. CONCLUSIONS: The results provide evidence for neurofunctional markers of COVID-induced SA and may help develop targeted brain-based interventions that reduce SA.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy is a common complication of diabetes mellitus. Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies. However, existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research. Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy, it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods. This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods. Various metabolic mechanisms (e.g., polyol, hexosamine, protein kinase C pathway) are associated with diabetic peripheral neuropathy, and researchers are looking for more effective treatments through these pathways.

Overlooked encounter process that affects physical behaviors of stabilized nanoscale zero-valent iron during in situ groundwater remediation.

Dynamic encountering between groundwater matrices and nanoscale zero-valent iron (NZVI) injected for in situ subsurface remediation affects NZVI's mobility and has not been well recognized. Polyacrylic acid (PAA)-stabilized NZVI (NZVI-PAA) and Mg(OH)2-coated NZVI (NZVI@Mg(OH)2) were investigated as representative NZVIs stabilized by enhanced electrostatic repulsion and reduced magnetic attraction, respectively. Encounters with divalent cations and humic acid (HA) induced the drastic aggregation and sedimentation (presedimentation) of NZVI-PAA owing to Lewis acid-base interactions and heteroaggregation. In addition, encountered groundwater electrolytes could not effectively provide electrostatic repulsion for NZVI-PAA, resulting in breakthrough ripening dynamics. The presedimentation and ripening behaviors of NZVI-PAA were eliminated and unheeded after mixing the NZVI slurry with groundwater by sonication. In comparison, the encountering process barely impacted NZVI@Mg(OH)2, for which settling was hindered. Although the particle-collector attraction promoted NZVI@Mg(OH)2 adsorption on pristine and hybrid-coated sands, the Langmuirian blocking dynamics of the NZVI@Mg(OH)2 breakthrough demonstrated its high mobility after adsorption sites of sand surface were exhausted. Extended Derjaguin-Landau-Verwey-Overbeek analysis and transport modeling provided insights into overlooked effects of encountering on physical behaviors of different stabilized NZVIs, which should be considered during practical applications under diverse subsurface conditions.

Depression and anxiety among caregivers of psychiatric patients during the late stage of the COVID-19 pandemic: A perspective from network analysis.

BACKGROUND: Depressive and anxiety symptoms (depression and anxiety hereafter) are common among psychiatric patients and their caregivers during the COVID-19 pandemic. Network analysis is a novel method to assess the associations between psychiatric syndromes/disorders at the symptom level. This study examined depression and anxiety among caregivers of psychiatric inpatients during the late stage of the COVID-19 pandemic from the perspective of network analysis. METHODS: A total of 1101 caregivers of psychiatric inpatients were included in this study. The severity of depression was assessed using the nine-item Patient Health Questionnaire (PHQ-9), while anxiety was assessed with the seven-item Generalized Anxiety Disorder Scale (GAD-7). The expected index (EI) and bridge EI index were used to identify the central and bridge symptoms, respectively. The stability of the network was evaluated via a case-dropping bootstrap procedure. RESULTS: The prevalence of depression and anxiety were 32.4 % (95%CI: 29.7 %-35.3 %) and 28.0 % (95%CI: 25.4 %-30.7 %), respectively while the prevalence of comorbid depression and anxiety was 24.9 % (95%CI: 22.4 %-27.6 %). The most central symptom was "Fatigue", followed by "Trouble Relaxing" and "Restlessness". The highest bridge symptom was "Restlessness", followed by "Uncontrollable worry" and "Suicide ideation". The bootstrap test indicated that the whole network model was stable, and no network difference was detected between genders and between different education levels. CONCLUSIONS: Depression, anxiety, and comorbid depression and anxiety were common among caregivers of psychiatric inpatients during the late stage of the COVID-19 pandemic. Central and bridge symptoms identified in this network analysis should be considered key target symptoms to address in caregivers of patients.

Functional characterization of two TolC in the resistance to drugs and metals and in the virulence of Riemerella anatipestifer.

IMPORTANCE: Riemerella anatipestifer (RA) is a notorious duck pathogen, characterized by a multitude of serotypes that exhibit no cross-reaction with one another. Moreover, RA is resistant to various antibacterial agents. Consequently, understanding the mechanisms behind resistance and identifying potential targets for drug development have become pressing needs. In this study, we show that the two TolC proteins play a role in the resistance to different drugs and metals and in the virulence. The results suggest that TolCA has a wider range of efflux substrates than TolCB. Except for gentamicin, neither TolCA nor TolCB was involved in the efflux of the other tested antibiotics. Strikingly, TolCA but not TolCB enhanced the frequency of resistance-conferring mutations. Moreover, TolCA was involved in RA virulence. Given its conservation in RA, TolCA has potential as a drug target for the development of therapeutics against RA infections.

CREB-induced LINC00473 promotes chemoresistance to TMZ in glioblastoma by regulating O6-methylguanine-DNA-methyltransferase expression via CEBPα binding.

Temozolomide (TMZ) offers substantial therapeutic benefits for glioblastoma (GB), yet its efficacy is hindered the development of chemoresistance. The role of long non-coding RNAs (lncRNAs) in tumorigenesis and chemoresistance has garnered great attention in studies on TMZ resistance. This study aimed to reveal the role of LINC00473 in TMZ chemoresistance and the underlying mechanism in GB. The expression of LINC00473 in TMZ-resistant and TMZ-sensitive GB cells was investigated using qPCR analysis. The role of LINC00473 in regulating TMZ resistance in GB cells was analyzed using the CCK-8 assay, colony formation assay, and flow cytometry. The next steps included assessing if LINC00473 is regulated by CREB and whether LINC00473 promotes chemoresistance through MGMT regulation via CEBPα. Further, chemoresistance delivery between cells via exosomal LINC00473 was validated in vitro and in vivo. Results showed that LINC00473 levels were elevated in TMZ-resistant cells upon CREB activation, and the lncRNA promoted the chemoresistance of GB cells through the upregulation of MGMT expression. Mechanistically, LINC00473 regulated the MGMT expression by binding to CEBPα. The highly-expressed LINC00473 packaged in exosomes transferred chemoresistance to the adjacent TMZ-sensitive GB cells. In conclusion, a novel CREB/LINC00473/CEBPα/MGMT pathway was revealed in the GB TMZ-resistance formation. In addition, an exosome-based mechanism of chemoresistance transmission was revealed, suggesting that LINC00473 could be used as a novel therapeutic target for GB.

Peimisine ameliorates DSS-induced colitis by suppressing Jak-Stat activation and alleviating gut microbiota dysbiosis in mice.

OBJECTIVES: Inflammatory cytokine secretion and gut microbiota dysbiosis play crucial roles in ulcerative colitis. In this research, the protective effects of peimisine on colitis mice were investigated. METHODS: The protective effects were evaluated by the disease activity index, colonic length, hematoxylin-eosin, and AB/PAS Staining. The protective mechanisms were analyzed by ELISA, Western-blot, immunohistochemistry staining, immunofluorescence staining, and 16S rRNA gene analysis. KEY FINDINGS: The results showed that peimisine treatment could reduce the disease activity index, prevent colonic shortening, and alleviate colon tissue damage. Peimisine treatment also decreased the levels of MCP-1, IL-1ß, IL-6, IFN-γ, TNF-α and affected macrophage polarization and Th17/Treg cell balance by downregulating the expression of jak1/2, p-jak1/2, stat1/3, and p-stat1/3. Moreover, peimisine treatment significantly increased the abundances of beneficial microbes (e.g. Ruminococcaceae UCG-014 and Lachnospiraceae_NK4A136_group) and decreased the abundances of harmful microbes (e.g. Bacteroides and Escherichia). CONCLUSIONS: Peimisine can ameliorate colitis by inhibiting Jak-Stat signaling pathway, reversing gut microbiota alterations, suppressing macrophage M1 polarization, maintaining the Th17/Treg cell balance, and reducing sustained inflammatory cytokines-related inflammatory injury.

Deep learning-based regional ECG diagnosis platform.

OBJECTIVE: To enable the intelligent diagnosis of a variety of common Electrocardiogram (ECG), we investigate the deep learning-based ECG diagnosis system. METHODS: From January 2015 to December 2019, four consecutive years of 100,120 conventional 12-lead ECG data were collected in our hospital. Utilizing this dataset, we constructed a deep learning model designed to intelligently diagnose prevalent ECG anomalies by employing a multi-task learning framework. The system performance was evaluated using various metrics, including sensitivity, specificity, negative predictive value, positive predictive value, and so forth. Additionally, we employed an ECG intelligent diagnostic platform for clinical application to undertake real-time online analysis of 2500 conventional 12-lead ECG samples in June 2020, aiming to validate our model. At this stage, we compared the performance of our model against the traditional manual identification method. RESULTS: The efficacy of the ECG intelligent diagnostic model was notably high for common and straightforward ECG patterns, such as sinus rhythm (F1 = 98.01%), sinus tachycardia (F1 = 96.26%), sinus bradycardia (F1 = 94.88%), and a normal electrocardiogram (F1 = 91.71%), as well as for Premature Ventricular Contractions (F1 = 91.62%). Nevertheless, when diagnosing rarer and more intricate ECG anomalies, the system requires an increased number of samples to refine the deep learning models. During the validation stage, our model exhibited better efficiency in terms of accuracy, labor time and labor cost when compared to the manual identification approach. CONCLUSIONS: Our deep learning-driven intelligent ECG diagnostic model clearly demonstrates significant clinical utility. The integrated artificial intelligence diagnosis system not only has the potential to augment physicians in their diagnostic processes but also offers a viable avenue to reduce associated labor costs.

ADHD in Narcolepsy: A Closer Look at Prevalence and Ties.

The reported prevalence of attention deficit hyperactivity disorder (ADHD) in narcolepsy varies considerably, while the associated factors remain inadequately established. A systematic search of studies published in PubMed, EMBASE, and the Cochrane Library was performed from inception to March 2023. Ten studies with 839 patients with narcolepsy were included in the study. Utilizing a random effects model, the pooled prevalence of ADHD in narcolepsy was 25% (95% CI, 14-38%). Notably, patients with narcolepsy type 2 showed a significantly higher prevalence of ADHD than that of narcolepsy type 1 (46% vs. 20%, p = 0.045). Furthermore, the rate of ADHD was notably elevated in narcolepsy compared with the healthy controls (odds ratio 9.59, 95% CI, 4.06-22.63, p < 0.001). Several factors such as excessive daytime sleepiness (EDS), fatigue, insomnia severity, and the quality of life were significantly associated with ADHD in narcolepsy (all ps < 0.05). These findings highlight the importance of monitoring and managing ADHD in narcolepsy, and provide a clue to help reducing ADHD by intervening in these associated factors.

LINC02532 by Mediating miR-541-3p/HMGA1 Axis Exerts a Tumor Promoter in Breast cancer.

The newly discovered LINC02532 is abnormally expressed in a variety of cancers and promotes cancer progression. The research proposed to discover the biological and molecular mechanisms of LINC02532 in breast cancer (BCa). In the resected BCa tissue samples and adjacent normal tissues, LINC02532, miR-541-3p, and High Mobility Group A1 (HMGA1) levels were determined. Cell function experiments were carried out on the premise of cell transfection with relevant plasmids. Based on that, the influence of LINC02532, miR-541-3p, and HMGA1 on MCF-7 cell activities (proliferation, migration, invasion, cell cycle, and apoptosis) was determined, as well as on EMT. Additionally, animal experiments were allowed to support cell experimental conclusions on LINC02532. Finally, the mechanistic network of LINC02532, miR-541-3p, and HMGA1 was identified. It was BCa tissues highly expressing LINC02532 and HMGA1, while lowly expressing miR-541-3p. Functionally, LINC02532 depletion repressed the activities and EMT process of MCF-7 cells. Silencing LINC02532 delayed tumor growth in mice. In terms of mechanism, LINC02532 mainly existed in the cytoplasm and could mediate HMGA1 expression by absorbing miR-541-3p. The findings offer new insights into the molecular mechanisms of LINC02532 in BCa and, more importantly, new strategies for the clinical treatment of BCa.

Targeted chemical profiling for p-HAP glycosides by using molecular networking and comparative analysis of their contents between Artemisia japonica and Artemisia capillaris.

A total of 65 phenolic acid compounds were annotated or identified by UHPLC-MS/MS method, among them, 17 p-HAP (p-hydroxyacetophenone) glycosides were firstly targeted profiled based on molecular networking. Their characteristic product ions of MS/MS spectra were found and examined on the guideline of targeted isolation. As a result, a new p-HAP glycoside was thus obtained and determined as 2'-O-caffeoyl-p-HAP-4-O-ß-D-glucopyranoside (33) based on 1D and 2D NMR data. Besides, multicomponents quantitative analysis indicated the distinct regional variability in chemicals distribution of A. japonica, and meanwhile, the contents of p-HAP glycosides from A. japonica were higher than those in A. capillaris as a whole, which further suggested the potential medicinal value of A. japonica.

Visually or auditorily induced seizures involve the activation of nonhippocampal brain areas and hippocampal removal does not alleviate seizures in a mouse model of temporal lobe epilepsy.

OBJECTIVE: Several studies have attributed epileptic activities in temporal lobe epilepsy (TLE) to the hippocampus; however, the participation of nonhippocampal neuronal networks in the development of TLE is often neglected. Here, we sought to understand how these nonhippocampal networks are involved in the pathology that is associated with TLE disease. METHODS: A kainic acid (KA) model of temporal lobe epilepsy was induced by injecting KA into dorsal hippocampus of C57BL/6J mice. Network activation after spontaneous seizure was assessed using c-Fos expression. Protocols to induce seizure using visual or auditory stimulation were developed, and seizure onset zone (SOZ) and frequency of epileptic spikes were evaluated using electrophysiology. The hippocampus was removed to assess seizure recurrence in the absence of hippocampus. RESULTS: Our results showed that cortical and hippocampal epileptic networks are activated during spontaneous seizures. Perturbation of these networks using visual or auditory stimulation readily precipitates seizures in TLE mice; the frequency of the light-induced or noise-induced seizures depends on the induction modality adopted during the induction period. Localization of SOZ revealed the existence of cortical and hippocampal SOZ in light-induced and noise-induced seizures, and the development of local and remote epileptic spikes in TLE occurs during the early stage of the disease. Importantly, we further discovered that removal of the hippocampi does not stop seizure activities in TLE mice, revealing that seizures in TLE mice can occur independent of the hippocampus. SIGNIFICANCE: This study has shown that the network pathology that evolves in TLE is not localized to the hippocampus; rather, remote brain areas are also recruited. The occurrence of light-induced or noise-induced seizures and epileptic discharges in epileptic mice is a consequence of the activation of nonhippocampal brain areas. This work therefore demonstrates the fundamental role of nonhippocampal epileptic networks in generating epileptic activities with or without the hippocampus in TLE disease.