Extracellular vesicles activated cancer-associated fibroblasts promote lung cancer metastasis through mitophagy and mtDNA transfer.

BACKGROUND: Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear. METHODS: The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry. RESULTS: Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis. CONCLUSIONS: These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis.

Advancing Hyperspectral and Multispectral Image Fusion: An Information-Aware Transformer-Based Unfolding Network.

In hyperspectral image (HSI) processing, the fusion of the high-resolution multispectral image (HR-MSI) and the low-resolution HSI (LR-HSI) on the same scene, known as MSI-HSI fusion, is a crucial step in obtaining the desired high-resolution HSI (HR-HSI). With the powerful representation ability, convolutional neural network (CNN)-based deep unfolding methods have demonstrated promising performances. However, limited receptive fields of CNN often lead to inaccurate long-range spatial features, and inherent input and output images for each stage in unfolding networks restrict the feature transmission, thus limiting the overall performance. To this end, we propose a novel and efficient information-aware transformer-based unfolding network (ITU-Net) to model the long-range dependencies and transfer more information across the stages. Specifically, we employ a customized transformer block to learn representations from both the spatial and frequency domains as well as avoid the quadratic complexity with respect to the input length. For spatial feature extractions, we develop an information transfer guided linearized attention (ITLA), which transmits high-throughput information between adjacent stages and extracts contextual features along the spatial dimension in linear complexity. Moreover, we introduce frequency domain learning in the feedforward network (FFN) to capture token variations of the image and narrow the frequency gap. Via integrating our proposed transformer blocks with the unfolding framework, our ITU-Net achieves state-of-the-art (SOTA) performance on both synthetic and real hyperspectral datasets.

Integrative analysis of the cuproptosis-related gene ATP7B in the prognosis and immune infiltration of IDH1 wild-type glioma.

Glioma is the most common malignant tumor in the brain and the central nervous system with a poor prognosis, and wild-type isocitrate dehydrogenase (IDH) glioma indicates a worse prognosis. Cuproptosis is a recently discovered form of cell death regulated by copper-dependent mitochondrial respiration. However, the effect of cuproptosis on tumor prognosis and immune infiltration is not clear. In this research, we analyzed of public databases to show the correlation between cuproptosis-related genes and the prognosis of IDH1 wild-type glioma. Nine out of 12 genes were upregulated in IDH1 wild-type glioma patients, and 6 genes were significantly associated with overall survival (OS), while 5 genes were associated with progression-free survival (PFS). Then, we constructed a prognostic cuproptosis-related gene signature for IDH1 wild-type glioma patients. ATP7B was considered an independent prognostic indicator, and a low expression level of ATP7B was related to a shorter period of OS and PFS. Moreover, downregulation of ATP7B was correlated not only with the infiltration of activated NK cells, CD8 + T cells and M2 macrophages; but also with high expression of immune checkpoint genes and tumor mutation burden (TMB). In the IDH1 wild-type glioma tissues we collected, our data also confirmed that high tumor grade was accompanied by low expression of ATP7B and high expression of PD-L1, which was associated with increasing infiltration of CD8 + immune cells. In conclusion, our research constructed a prognostic cuproptosis-related gene signature model to predict the prognosis of IDH1 wild-type glioma. ATP7B is deemed to be a potential prognostic indicator and novel immunotherapy biomarker for IDH1 wild-type glioma patients.

[Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma].

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

The effectiveness of Interpersonal Psychotherapy-Adolescent Skills Training for adolescents with depression: a systematic review and meta-analysis.

Background: Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is a standardized depression prevention program for adolescents conducted in campus settings. The purpose of this review is to examine the randomized controlled trials of IPT-AST for the prevention of adolescent depression in the past 20 years. Methods: A systematic search of relevant electronic databases (PubMed, WOS, Embase, PsycINFO, the Cochrane Library, CNKI and WANFANG DATA) and study reference lists was conducted. Any study investigating the effectiveness of IPT-AST in 12- to 20-year-olds with depressive symptoms was eligible. Synthesis was via narrative summary and meta-analysis. Results: A total of 6 studies met the inclusion criteria. Meta-analysis results showed a remarkable improvement in patients' depressive symptoms after IPT-AST intervention (WMD = -5.05, 95% CI = -8.11 to -1.98, p < 0.05, I2 = 77%). Six month follow-up data showed that the intervention outcomes of IPT-AST remained significant (WMD = -3.09, 95% CI: -5.23 to -0.94, p < 0.05, I2 = 57%). Conclusion: This meta-analysis showed that IPT-AST was effective in adolescents with depressive symptoms at post-prevention and at 6-month follow-up. However, these conclusions are cautious, as they are based on a small number of studies and the presence of author duplication. Future studies should use multi-center, large-sample randomized controlled trials to evaluate the efficacy of IPT-AST for preventing depression in adolescents. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023393047.

Non-Coding RNAs Derived from Extracellular Vesicles Promote Pre-Metastatic Niche Formation and Tumor Distant Metastasis.

Metastasis is a critical stage of tumor progression, a crucial challenge of clinical therapy, and a major cause of tumor patient death. Numerous studies have confirmed that distant tumor metastasis is dependent on the formation of pre-metastatic niche (PMN). Recent studies have shown that extracellular vesicles (EVs) play an important role in PMN formation. The non-coding RNAs (ncRNAs) derived from EVs mediate PMN formation and tumor-distant metastasis by promoting an inflammatory environment, inhibiting anti-tumor immune response, inducing angiogenesis and permeability, and by microenvironmental reprogramming. Given the stability and high abundance of ncRNAs carried by EVs in body fluids, they have great potential for application in tumor diagnosis as well as targeted interventions. This review focuses on the mechanism of ncRNAs derived from EVs promoting tumor PMN formation and distant metastasis to provide a theoretical reference for strategies to control tumor metastasis.

HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma.

Studies have shown that acetylation modification plays an important role in tumor proliferation and metastasis. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is downregulated in certain tumors, as a tumor suppressor role. However, the regulation of LHPP expression and its function in nasopharyngeal carcinoma (NPC) remain unclear. In the present study, we found that LHPP was downregulated in NPC, and overexpression of LHPP inhibited the proliferation and invasion of NPC cells. Mechanistically, HDAC4 deacetylated LHPP at K6 and promoted the degradation of LHPP through TRIM21 mediated K48-linked ubiquitination. HDAC4 was confirmed to be highly expressed in NPC cells and promoted the proliferation and invasion of NPC cells through LHPP. Further research found that LHPP could inhibit the phosphorylation of tyrosine kinase TYK2, thereby inhibiting the activity of STAT1. In vivo, knockdown of HDAC4 or treatment with small molecule inhibitor Tasquinimod targeting HDAC4 could significantly inhibit the proliferation and metastasis of NPC by upregulating LHPP. In conclusion, our finding demonstrated that HDAC4/LHPP signal axis promotes the proliferation and metastasis of NPC through upregulating TYK2-STAT1 phosphorylation activation. This research will provide novel evidence and intervention targets for NPC metastasis.

Identification of Ferroptosis-Related Genes in Schizophrenia Based on Bioinformatic Analysis.

The purpose of this study is to explore the correlation between ferroptosis-related genes and schizophrenia in order to explore the new direction of diagnosis and treatment of schizophrenia. We screened the datasets related to schizophrenia from the Gene Expression Comprehensive Database (GEO) and obtained ferroptosis-related genes from the FerrDB database. Bioinformatics methods were used to analyze differentially expressed genes (DEGs) and genes associated with ferroptosis-related between schizophrenia patients and healthy controls. On this basis, the hub genes were finally screened by enrichment analysis and PPI interaction analysis. Hub genes associated with ferroptosis were validated using other schizophrenia datasets in the GEO database. Finally, the hub gene-microRNA (miRNA), gene-transcription factor interaction network was constructed, and three ferroptosis-related hub genes (TP53, VEGFA and PTGS2) were screened. The validation results of these three genes in other datasets also support this conclusion. A miRNA: hsa-mir-16-5p was found to be related to the three hub genes, and pPHF8, SAP30 and lKDM5B were identified as common regulators of the three hub genes. Our results indicate that TP53, VEGFA and PTGS2 are significantly associated with schizophrenia, and may be ferroptosis-related markers of the disease.

A sectoral-level analysis of the short- and long-term impacts of the COVID-19 pandemic on China's stock market volatility.

Sampling China's Shenyin & Wanguo Sectoral Indices for 28 industries and 3272 listed firms included in those indices, and using industry- and firm-level daily data up to December 31, 2020, this paper empirically examined the short- and long-run impacts of the COVID-19 pandemic on stock return volatility. The results of the event study and univariate graphic analysis suggested that the market volatilities of the 28 industries were affected by COVID-19 events at various levels and that the events increased the volatility continuously for up to 6 days. The results of the panel data regression models revealed that the COVID-19-related daily new confirmed cases, daily new deaths, and cumulative cured cases were associated with higher volatility for all industries, although the impact levels were small; the daily deaths impacted volatility more than confirmed and cured cases. Finally, positive and significant effects of firm-specific variables such as total assets, turnover ratio and trading volume were recorded, indicating that fundamental aspects of the company and investors' behaviour also made great sense.

Exploring the Core Genes of Schizophrenia Based on Bioinformatics Analysis.

Schizophrenia is a clinical syndrome composed of a group of symptoms involving many obstacles such as perception, thinking, emotion, behavior, and the disharmony of mental activities. Schizophrenia is one of the top ten causes of disability globally, accounting for about 1% of the global population. Previous studies have shown that schizophrenia has solid genetic characteristics. However, the diagnosis of schizophrenia mainly depends on symptomatic manifestations, and no gene can be used as a clear diagnostic marker at present. This study explored the hub genes of schizophrenia by bioinformatics analysis. Three datasets were selected and downloaded from the GEO database (GSE53987, GSE21138, and GSE27383). GEO2R, NCBI's online analysis tool, is used to screen out significant gene expression differences. The genes were functionally enriched by GO and KEGG enrichment analysis. On this basis, the hub genes were explored through Cytoscape software, and the immune infiltration analysis and diagnostic value of the screened hub genes were judged. Finally, four hub genes (NFKBIA, CDKN1A, BTG2, GADD45B) were screened. There was a significant correlation between two hub genes (NFKBIA, BTG2) and resting memory CD4 T cells. The ROC curve results showed that all four hub genes had diagnostic value.

Protective role of Dihydromyricetin in Alzheimer's disease rat model associated with activating AMPK/SIRT1 signaling pathway.

The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer's disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.

Cobweb-like Structural Stimuli-Responsive Composite with Oil Warehouse and Transportation System for Oil Storage and Recyclable Smart-Lubrication.

Despite recent advances in the stimuli-responsive composites for oil storage and smart lubrication, achieving the high oil storage and recyclable smart-lubrication remains a challenge. Herein, a novel cobweb-like structural system consisting of oil warehouse and transportation system was designed and prepared and it shows high capacity of oil storage and recyclable smart-lubrication. Hollow SiO2 microspheres grated of KH550 and porous polyimide (PPI) were used as oil warehouse and pipeline, respectively, to build the smart system. Because of the novel structure, the composites can keep both high oil-content and oil-retention. Applying stimuli on materials resulted in lubricants releasing on the contact surface which can reduce the friction and wear during sliding. However, removing stimuli, the capillary force induced the sucking back of lubricant into the interior of composites through interconnected small pores of PPI. On the basis of high oil storage and stimuli-responsive performance, the composites can be used for recyclable smart-lubrication. The composites showed remarkable lubricating properties (coefficient of friction 0.056 and Ws 3.55 × 10-7 mm3 N-1 m-1) when the content of KHSM (hollow silica microspheres grated of KH550 (3-Aminopropyltriethoxysilane)) was 1.5 wt % by subjecting it to macroscopic pin-on-disc friction tests. Therefore, cobweb-like structural composites with oil warehouse and transportation system hold the promise for formulating of high oil storage and recyclable smart-lubrication.

Histone deacetylase-2 is involved in stress-induced cognitive impairment via histone deacetylation and PI3K/AKT signaling pathway modification.

Exposure to chronic stress upregulates blood glucocorticoid levels and impairs cognition via diverse epigenetic mechanisms, such as histone deacetylation. Histone deacetylation can lead to transcriptional silencing of many proteins involved in cognition and may also cause learning and memory dysfunction. Histone deacetylase­2 (HDAC2) has been demonstrated to epigenetically block cognition via a reduction in the histone acetylation level; however, it is unknown whether HDAC2 is involved in the cognitive decline induced by chronic stress. To the best of authors' knowledge, this is the first study to demonstrate that the stress hormone corticosteroid upregulate HDAC2 protein levels in neuro­2a cells and cause cell injuries. HDAC2 knockdown resulted in a significant amelioration of the pathological changes in N2a cells via the upregulation of histone acetylation and modifications in the phosphoinositide 3­kinase/protein kinase B signaling pathway. In addition, the HDAC2 protein levels were upregulated in 12­month­old female C57BL/6J mice under chronic stress in vivo. Taken together, these findings suggested that HDAC2 may be an important negative regulator involved in chronic stress­induced cognitive impairment.