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Schizophrenia is a chronic mental disorder characterized by continuous or relapsing episodes of psychosis. While previous studies have detected functional network connectivity alterations in patients with schizophrenia, and most have focused on static functional connectivity. However, brain activity is believed to change dynamically over time. Therefore, we computed dynamic functional network connectivity using the sliding window method in 38 patients with schizophrenia and 31 healthy controls. We found that patients with schizophrenia exhibited higher occurrences in the weakly and sparsely connected state (state 3) than healthy controls, positively correlated with negative symptoms. In addition, patients exhibited fewer occurrences in a strongly connected state (state 4) than healthy controls. Lastly, the dynamic functional network connectivity between the right executive-control network and the medial visual network was decreased in schizophrenia patients compared to healthy controls. Our results further prove that brain activity is dynamic, and that alterations of dynamic functional network connectivity features might be a fundamental neural mechanism in schizophrenia.

Background This study evaluated the utility of serum NR1 and NR2 concentrations in identifying individuals with first-episode schizophrenia (FES) and clinical high risk (CHR) as well as their correlations with clinical symptoms and cognitive domains. Methods This cross-sectional study compared peripheral blood NR1 and NR2 concentrations among the FES, CHR, and healthy control (HC) groups and examined their association with cognitive function. Serum concentrations of NR1 and NR2 subunits were measured using ELISA, and cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Concentrations were compared among groups using the analysis of covariance or non-parametric tests and ROC curve analysis, and correlation was determined using the Pearson or Spearman method. Results A total of 41 FES cases, 34 CHR cases, and 41 HC were included in the study. Serum NR1 concentrations significantly varied among the three groups (Z = 16.19, P  < 0.001) and were significantly different between the FES group and the CHR (Z = -4.04, P  < 0.001) and HC groups (Z = -2.49, P  = 0.01). Additionally, serum NR2 concentration was significantly different between the CHR and HC groups (F = 5.37, P  = 0.02). In the FES group, serum NR1 concentration was negatively correlated with speed of processing ( r  = -0.41, P  = 0.02), whereas serum NR2 concentration was negatively correlated with verbal learning ( r  = -0.40, P  = 0.02). In the CHR group, serum NR1 concentration was positively correlated with the total MCCB score ( r  = 0.40, P  = 0.04). ROC curve analysis showed that NR2 level was better for discriminating FES (AUC: 69%; sensitivity: 56%; specificity: 85%; optimal cutoff value: 32.80 ng/mL) and CHR (AUC: 74%; sensitivity: 62%; specificity: 85%; optimal cutoff value: 32.77 ng/mL). Conclusions Serum NR1 and NR2 concentrations show potential for early identification of individuals with psychosis, but further validation is needed, and they are also correlated with cognition. Furthermore, serum NR2 concentration is more stable and serves as a promising objective biomarker for quantitative assessment.

LXR-623 (WAY-252623), a liver X receptor agonist, reduces atherosclerotic plaque progression and remarkably inhibits the proliferation of glioblastoma cells, owing to its brain-penetrant ability. However, the role of LXR-623 against the proliferation of other cancer cells and the underlying mechanism remain unknown. Long non-coding RNAs (lncRNAs) serve as novel and crucial regulators that participate in cancer tumorigenesis and diverse biological processes. Here, we report a previously uncharacterized mechanism underlying lncRNA-mediated exocytosis of LXR-623 via the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT)/p53 axis to suppress the proliferation of cancer cells in vitro. We found that LXR-623 significantly inhibited the proliferation and induced apoptosis and cell cycle arrest at S phase in breast cancer cells in a concentration- and time-dependent manner. Experiments using a xenograft mouse model revealed the inhibitory effects of LXR-623 on tumor growth. We used lncRNA microarray to investigate the potential genes regulated by LXR-623. As a result, LINC01125 was found to be significantly upregulated in the cells treated with LXR-623. Gain- and loss-of-function assays were conducted to investigate the anti-proliferation role of LINC01125. LINC01125 knockdown resulted in the inhibition of the cytotoxic effect of LXR-623; in contrast, LINC01125 overexpression significantly enhanced the effect of LXR-623. LXR-623 and LINC01125-mediated anti-growth regulation is, at least in part, associated with the participation of the PTEN/AKT/mouse double minute 2 homolog (MDM2)/p53 pathway. In addition, SF1670, a specific PTEN inhibitor with prolonged intracellular retention, may strongly block the anti-proliferation effect induced by LXR-623 and LINC01125 overexpression. Chromatin immunoprecipitation (ChIP) assay results suggest that p53 binds to the promoter of LINC01125 to strengthen the expression of the PTEN/AKT pathway. Taken together, our findings suggest that LXR-623 possesses significant antitumor activity in breast cancer cells that is partly mediated through the upregulation in LINC01125 expression and enhancement in apoptosis via the PTEN/AKT/MDM2/p53 pathway.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) poses significant health risks to poultry and humans, with biofilm formation often complicating treatment by enhancing bacterial persistence and resistance. Understanding the genetic mechanisms underlying this lifestyle transition is crucial for controlling infections. This study aimed to investigate the effect of biofilm formation on the transcriptional expression of specific biofilm- and virulence-associated genes in chicken-derived ExPEC strains. Methods: Biofilm formation conditions for three strong biofilm-producing chicken-derived ExPEC strains were optimized using an orthogonal experimental design (L9(33)), evaluating culture medium, incubation time, and initial inoculum concentration. Biofilm biomass was quantified via crystal violet staining. Subsequently, the transcription levels of 10 biofilm-associated genes and 17 virulence-associated genes were compared between planktonic and biofilm states using Reverse Transcription-quantitative PCR (RT-qPCR). Results: Optimal culture conditions varied among strains, though nutrient-rich media consistently promoted rapid biofilm formation. Transcriptional analysis revealed significant reprogramming in the biofilm state. Among biofilm-associated genes, flhC, tolA, qseC, mhpB, and bdcR were consistently and significantly upregulated across all strains (p < 0.05). Regarding virulence determinants, the expression of eaeA, LT, fimH, ompF, and iss was significantly upregulated (p < 0.05), whereas Sta levels were significantly reduced (p < 0.05). Conclusions: Biofilm formation induces a distinct transcriptional shift in chicken-derived ExPEC, simultaneously enhancing the expression of key genes involved in biofilm maintenance and pathogenicity. The conserved upregulation of flhC, tolA, qseC, mhpB, and bdcR suggests these genes are critical drivers of biofilm development. Consequently, they represent potential targets for novel therapeutic strategies aimed at preventing E. coli infections and eradicating biofilms in clinical and agricultural settings.

Stocking of filter-feeding fish (mainly Hypophthalmichthys molitrix and Aristichthys nobilis ) is a common method used in lakes and reservoirs in (sub)tropical China to control phytoplankton, but the results are ambiguous and lack long-term data to support. We analysed a decade (2010-2020) of monitoring data from a subtropical plateau reservoir, southwest China, to which filter-feeding fish were stocked annually. We found that the total phytoplankton biomass, cyanobacteria biomass and average individual mass of phytoplankton decreased significantly during the study period despite absence of nutrient concentration reduction. However, the grazing pressure of zooplankton on phytoplankton also decreased markedly as judged from changes in the ratio of zooplankton biomass to phytoplankton biomass and Daphnia proportion of total zooplankton biomass. This is likely a response to increasing predation on zooplankton by the stocked fish. Our results also indicated that water temperature, total phosphorus and water level promoted phytoplankton growth. Our results revealed that filter-feeding fish contributed to the decline in the biomass of phytoplankton but that it also had a strong negative effect on the grazing pressure of zooplankton on phytoplankton, even in this deep reservoir where zooplankton may have a better chance of survival through vertical migration. The particular strong effect on zooplankton is most likely due to imbalance of stocking and harvesting of fish. In the management of eutrophic reservoirs, the reduction of external nutrient loading should have highest priority. In highland (low temperature) deep-water eutrophic reservoirs, stocking of filter-feeding fish may help to control filamentous phytoplankton provided that the fish stocking is properly managed. The optimal stocking intensity of filter-feeding fish that can help control phytoplankton in such reservoirs without excessive impact on large-bodied zooplankton is a topic for further elucidation, however.

Dual leucine zipper kinase (DLK, Map3k12) is an axonal protein that governs the balance between degeneration and regeneration through its downstream effectors c-jun N-terminal kinase (JNK) and phosphorylated c-jun (p-c-Jun). In peripheral nerves DLK is generally inactive until induced by injury, after which it transmits signals to the nucleus via retrograde transport. Here we report that in contrast to this mode of regulation, in the uninjured adult mouse cerebellum, DLK constitutively drives nuclear p-c-Jun in cerebellar granule neurons, whereas in the forebrain, DLK is similarly expressed and active, but nuclear p-c-Jun is undetectable. When neurodegeneration results from mutant human tau in the rTg4510 mouse model, p-c-Jun then accumulates in neuronal nuclei in a DLK-dependent manner, and the extent of p-c-Jun correlates with markers of synaptic loss and gliosis. This regional difference in DLK-dependent nuclear p-c-Jun accumulation could relate to differing levels of JNK scaffolding proteins, as the cerebellum preferentially expresses JNK-interacting protein-1 (JIP-1), whereas the forebrain contains more JIP-3 and plenty of SH3 (POSH). To characterize the functional differences between constitutive- versus injury-induced DLK signaling, RNA sequencing was performed after DLK inhibition in the cerebellum and in the non-transgenic and rTg4510 forebrain. In all contexts, DLK inhibition reduced a core set of transcripts that are associated with the JNK pathway. Non-transgenic forebrain showed almost no other transcriptional changes in response to DLK inhibition, whereas the rTg4510 forebrain and the cerebellum exhibited distinct differentially expressed gene signatures. In the cerebellum, but not the rTg4510 forebrain, pathway analysis indicated that DLK regulates insulin growth factor-1 (IGF1) signaling through the transcriptional induction of IGF1 binding protein-5 (IGFBP5), which was confirmed and found to be functionally relevant by measuring signaling through the IGF1 receptor. Together these data illuminate the complex multi-functional nature of DLK signaling in the central nervous system (CNS) and demonstrate its role in homeostasis as well as tau-mediated neurodegeneration.

Nasopharyngeal carcinoma (NPC) is the most common cancer type originating in the nasopharynx, and varies notably from other cancer types of the head and neck in its occurrence, causes, clinical behavior and treatment. Significant effort has been made into understanding the biological properties of circulating tumor cells (CTCs), with previous studies demonstrating the critical role CTCs serve in the metastatic spread of carcinoma. However, associations between NPC and CTCs have not been completely elucidated. Therefore, in the present study, the CanPatrol™ CTC-enrichment technique and classical in situ hybridization assay were utilized to acquire, identify and classify CTCs from patients with NPC. Subsequently, the correlation between CTCs and the clinical indexes, progression-free survival (PFS), N-cadherin gene expression and the response to therapy were investigated. The present study then determined whether the Wnt/β-catenin signaling pathway served a role in therapy for NPC cells. Collectively, the research demonstrated that CTCs could be detected in patients with NPC. Additionally, CTCs exhibited a statistically significant association with the Epstein-Barr virus infection prior to therapy and Eastern Cooperative Oncology Group score following therapy. Furthermore, co-treatment with cisplatin and paclitaxel significantly decreased the number of CTCs. In addition, mesenchymal CTCs may serve as a predictor of PFS. Finally, the present study demonstrated that cisplatin combined with paclitaxel induced apoptosis and decreased the tumor markers in NPC cells through the Wnt/β-catenin signaling pathway. In conclusion, these data indicated that CTCs may serve as a biomarker in monitoring the therapeutic efficacy of treatments for NPC. Furthermore, the Wnt/β-catenin signaling pathway served a therapeutic role in the treatment of NPC.