Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice.

Background: Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer's disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly. Methods: In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia. Results: The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells. Conclusion: Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

Healthcare-seeking behaviours of patients with acute respiratory infection: a cross-sectional survey in a rural area of southwest China.

OBJECTIVES: This study aimed to assess the healthcare-seeking behaviour and related factors of people with acute respiratory symptoms in the rural areas of central and western China to estimate the disease burden of influenza more accurately. DESIGN: Cross-sectional survey. SETTINGS: Fifty-two communities/villages in the Wanzhou District, Chongqing, China, a rural area in southwest China, from May 2022 to July 2022. PARTICIPANTS: The participants were those who had been living in Wanzhou District continuously for more than 6 months and consented to participate. OUTCOME MEASURES: A semistructured questionnaire was used to determine the healthcare-seeking behaviour of participants, and the dichotomous response of 'yes' or 'no' was used to assess whether participants had acute respiratory symptoms and their healthcare-seeking behaviour. RESULTS: Only 50.92% (360 of 707) of the patients with acute respiratory infection visited medical and health institutions for treatment, whereas 49.08% (347 of 707) avoided treatment or opted for self-medication. The primary reason for not seeing a doctor was that patients felt their condition was not serious and visiting a medical facility for treatment was unnecessary. Short distance (87.54%) and reasonable charges (49.48%) were ranked as the most important reasons for choosing treatment at primary medical and health facilities (80.27%). The primary reasons for which patients visited secondary and tertiary hospitals (7.78% and 8.61%, respectively) were that doctors in such facilities were better at diagnosis (57.14%) and at treatment (87.10%). CONCLUSION: The findings provided in this study indicated that regular healthcare-seeking behaviour investigations should be conducted. The disease burden of influenza can be calculated more accurately when healthcare-seeking behaviour investigations are combined with surveillance in the hospitals.

Quantifying the Magnetic Interactions Governing Chiral Spin Textures Using Deep Neural Networks.

The interplay of magnetic interactions in chiral multilayer films gives rise to nanoscale topological spin textures that form attractive elements for next-generation computing. Quantifying these interactions requires several specialized, time-consuming, and resource-intensive experimental techniques. Imaging of ambient domain configurations presents a promising avenue for high-throughput extraction of parent magnetic interactions. Here, we present a machine learning (ML)-based approach to simultaneously determine the key magnetic interactions─symmetric exchange, chiral exchange, and anisotropy─governing the chiral domain phenomenology in multilayers, using a single binarized image of domain configurations. Our convolutional neural network model, trained and validated on over 10,000 domain images, achieved R2 > 0.85 in predicting the parameters and independently learned the physical interdependencies between magnetic parameters. When applied to microscopy data acquired across samples, our model-predicted parameter trends are consistent with those of independent experimental measurements. These results establish ML-driven techniques as valuable, high-throughput complements to conventional determination of magnetic interactions and serve to accelerate materials and device development for nanoscale electronics.

LRRC8A promotes the initial development of oxaliplatin resistance in colon cancer cells.

Leucine-rich repeat-containing 8 A (LRRC8A) is an essential component of the volume-regulated anion channel (VRAC), which plays a vital role in cell proliferation, migration, apoptosis, and drug resistance. In this study, we investigated the effects of LRRC8A on oxaliplatin resistance in colon cancer cells. The cell viability was measured after oxaliplatin treatment with cell counting kit-8 (CCK8) assay. RNA sequencing was used to analyze the differentially expressed genes (DEGs) between HCT116 and oxaliplatin-resistant HCT116 cell line (R-Oxa) cells. CCK8 assay and apoptosis assay indicated that R-Oxa cells significantly promoted drug resistance to oxaliplatin compared with native HCT116 cells. R-Oxa cells, deprived of oxaliplatin treatment for over six months (R-Oxadep), maintained a similar resistant property as R-Oxa cells. The LRRC8A mRNA and protein expression were markedly increased in both R-Oxa and R-Oxadep cells. Regulation of LRRC8A expression affected the resistance to oxaliplatin in native HCT116 cells, but not R-Oxa cells. Furthermore, The transcriptional regulation of genes in the platinum drug resistance pathway may contribute to the maintenance of oxaliplatin resistance in colon cancer cells. In conclusion, we propose that LRRC8A promotes the acquisition rather than the maintenance of oxaliplatin resistance in colon cancer cells.

Epigenetic and transcriptomic alterations in the ClC-3-deficient mice consuming a normal diet.

Introduction: Metabolic disorders are an important health concern that threatens life and burdens society severely. ClC-3 is a member of the chloride voltage-gated channel family, and ClC-3 deletion improved the phenotypes of dysglycemic metabolism and the impairment of insulin sensitivity. However, the effects of a healthy diet on transcriptome and epigenetics in ClC-3-/- mice were not explained in detail. Methods: Here, we performed transcriptome sequencing and Reduced Representation Bisulfite Sequencing for the liver of 3 weeks old WT and ClC-3-/- mice consuming a normal diet to insight into the epigenetic and transcriptomic alterations of ClC-3 deficient mice. Results: In the present study, we found that ClC-3-/- mice that were younger than 8 weeks old had smaller bodies compared to ClC-3+/+ mice with ad libitum self-feeding normal diet, and ClC-3-/- mice that were older than 10 weeks old had a similar body weight. Except for the spleen, lung, and kidney, the average weight of the heart, liver, and brain in ClC-3-/- mice was lower than that in ClC-3+/+ mice. TG, TC, HDL, and LDL in fasting ClC-3-/- mice were not significantly different from those in ClC-3+/+ mice. Fasting blood glucose in ClC-3-/- mice was lower than that in ClC-3+/+ mice; the glucose tolerance test indicated the response to blood glucose increasing for ClC-3-/- mice was torpid, but the efficiency of lowering blood glucose was much higher once started. Transcriptomic sequencing and reduced representation bisulfite sequencing for the liver of unweaned mice indicated that ClC-3 deletion significantly changed transcriptional expression and DNA methylation levels of glucose metabolism-related genes. A total of 92 genes were intersected between DEGs and DMRs-targeted genes, of which Nos3, Pik3r1, Socs1, and Acly were gathered in type II diabetes mellitus, insulin resistance, and metabolic pathways. Moreover, Pik3r1 and Acly expressions were obviously correlated with DNA methylation levels, not Nos3 and Socs1. However, the transcriptional levels of these four genes were not different between ClC-3-/- and ClC-3+/+ mice at the age of 12 weeks. Discussion: ClC-3 influenced the methylated modification to regulate glucose metabolism, of which the gene expressions could be driven to change again by a personalized diet-style intervention.

Secoisolariciresinol Diglucoside Exerts Anti-Inflammatory and Antiapoptotic Effects through Inhibiting the Akt/IκB/NF-κB Pathway on Human Umbilical Vein Endothelial Cells.

Inflammation is a key regulator in the progression of atherosclerosis (AS) which extremely affects people's health. Secoisolariciresinol diglucoside (SDG), a plant lignan, is relevant to angiogenesis and cardioprotection against ischemia-reperfusion injury and improves vascular disorders. However, the effect of SDG on cardiovascular disorder is not clear. In the present study, we aimed to investigate the effects of SDG on lipopolysaccharide- (LPS-) stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and elucidate the underlying mechanism. The LPS-stimulated HUVEC cellular model was established. The cell viability, the cell tube formation activity, the nitric oxide (NO) release, the levels of inflammatory cytokine interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the activation of nuclear factor kappa-B (NF-κB) pathway, and the expression of protein kinase B (Akt) were determined using Cell Counting Kit-8, cell tube-formation assay, western blotting, and enzyme-linked immunosorbent assay. Our results revealed that SDG reduces the angiogenic capacity of HUVECs and inhibited LPS-mediated HUVEC injury and apoptosis. In addition, SDG increased NO release and decreased the levels of IL-1ß, IL-6, and TNF-α in LPS-treated HUVECs. Meanwhile, SDG inhibited the NF-κB pathway and downregulated Akt expression in LPS-induced HUVECs. Our results indicated that SDG relieves LPS-mediated HUVEC injury by inhibiting the NF-κB pathway which is partly dependent on the disruption of Akt activation. Therefore, SDG exerts its cytoprotective effects in the context of LPS-treated HUVECs via regulation of the Akt/IκB/NF-κB pathway and may be a potential treatment drug for cardiovascular disease.