In Situ Synthesis of Liquid Metal Conductive Fibers toward Smart Cloth.

To meet the diverse needs of humans, smart cloth has become a potential research hotspot to replace traditional cloth. However, it is challenging to manufacture a flexible fabric with multiple functions. Here, we introduce a smart cloth based on liquid metal (LM) conductive fibers. Ga2O3 nanoparticles are obtained through ultrasonic pretreatment. Furthermore, a coordination bond is formed between thiol groups on the surface of protein fibers and Ga2O3 through a scraping method, allowing Ga2O3 particles to be grafted onto the surface of protein fibers in situ. Finally, LM conductive fibers are encapsulated using a photocuring adhesive. In addition, a wearable smart cloth integrated with multiple sensors has been developed based on LM conductive fibers. Users can not only monitor their movement trajectory and the surrounding environment in real time but also have their data supervised by family members through a client, achieving remote and continuous monitoring. The development of this wearable smart cloth provides strong support for future wearable, flexible electronic devices.

The roles of long non-coding RNAs in Alzheimer's disease diagnosis, treatment, and their involvement in Alzheimer's disease immune responses.

Alzheimer's disease (AD) is the most frequent type of dementia, presenting a substantial danger to the health and well-being of the aged population. It has arisen as a significant public health problem with considerable socioeconomic repercussions. Unfortunately, no effective treatments or diagnostic tools are available for Alzheimer's disease. Despite substantial studies on the pathophysiology of Alzheimer's, the molecular pathways underpinning its development remain poorly understood. Long non-coding RNAs (lncRNAs) vary in size from 200 nucleotides to over 100 kilobytes and have been found to play critical roles in various vital biological processes that play critical in developing Alzheimer's disease. This review intends to examine the functions of long non-coding RNAs in diagnosing and treating Alzheimer's disease and their participation in immunological responses associated with AD.

Denoised single-pixel imaging in a Fourier acquisition mode.

The degradation of imaging quality caused by environmental noise during Fourier single pixel imaging (FSPI) is a big problem. In this paper, we propose simple and efficient denoised single-pixel imaging schemes by using linear filters to reduce the impact. Two filters, such as an average filter and Gaussian filter, are employed, and their corresponding schemes are named SCH-A and SCH-G, respectively. The experimental and simulation results show that both schemes can effectively reduce the impact of environmental noise and have greater robustness in comparison with those using the deringing SPI and conventional SPI. Compared with SCH-A, the reconstructed image by SCH-G keeps more details and edges. With the increase of template size, SCH-A and SCH-G have better filtering effects with the same variance. Meanwhile, the larger the template size is, the better filtering effect SCH-A has. This conclusion is also applicable to SCH-G under the same variance.

Inhibition of Alzheimer's disease by 4-octyl itaconate revealed by RNA-seq transcriptome analysis.

AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.

Excellent Oxygen Barrier Property of Unfilled Natural Rubber/trans-Butadiene-co-Isoprene Rubber Vulcanizates under the Synergistic Effect of Crosslinking Density and Crystallization.

The thermo-oxidative aging of rubber products is inevitable during their use and leads to product failure and can even endanger safety. Oxygen is an important factor that cannot be ignored during the thermo-oxidative aging process. Thus, the gas barrier property of rubber products is of significant concern. In this work, a strategy of crystallizing rubber in unfilled rubber composites was designed by firstly constructing a dual synergistic mechanism of crosslinking density and crystallization on the oxygen barrier properties. As a crystallizable polymer, trans-butadiene-co-isoprene rubber (TBIR) shows dendritic fibril crystals or spherulites in natural rubber (NR)/TBIR vulcanizates. Meanwhile, the vulcanizates containing TBIR have a higher crosslinking density than NR vulcanizates. These TBIR-rich crystals and high-crosslinking-density structures are distributed in vulcanizates like continuous islands. Contrary to what has been reported in the literature, the decrease in oxygen permeability of NR/TBIR is not only due to the high crosslinking density and free volume of the polymer matrix, but more importantly, the spherulites of TBIR play a role in blocking and prolonging the oxygen diffusion path during the diffusion of oxygen in the polymer composites. We propose that the compatible crystalline polymer can replace the lamellar filler, play the role of the oxygen barrier in rubber composites, reduce the diffusion and dissolution of oxygen, and achieve the effect of improving the thermo-oxidative aging property of the rubber composite. Future research will follow the morphology evolution of TBIR crystals, their crosslinking structure and density, and interactions between TBIR and NR on the oxygen barrier and thermo-oxidative aging property.

Predicting cancer-specific mortality in T1/2 hepatocellular carcinoma after radiofrequency ablation by competing risk nomogram: A population-based analysis.

BACKGROUND: Radiofrequency ablation (RFA) is one of the primary treatment methods for T1/2 hepatocellular carcinoma (HCC), but the risk factors after RFA remain controversial. This study aims to identify the key factors associated with cancer-specific mortality (CSM) in patients with T1/2 HCC after RFA using competing risk analysis and to establish a prognostic nomogram for improved clinical management. METHODS: A total of 2,135 T1/2 HCC patients treated with RFA were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and randomly categorized into training and validation sets. Univariate and multivariable competing risk analyses were performed to identify risk factors associated with CSM and construct a competing risk nomogram. Receiver operating characteristic (ROC) curves, concordance indices (C-indexes), calibration plots, and decision curve analysis (DCA) were conducted to evaluate the predictive efficiency and clinical applicability of the nomogram in the training and validation sets. Patients were stratified according to their nomogram score, and the different risk groups were compared using cumulative incidence function (CIF) curves and Gray's validation . RESULTS: The 5-year CSM rate for HCC patients treated with RFA was 30.1 %. Grade, tumor size, tumor number, cirrhosis, and AFP level were identified as independent risk factors for CSM. A prognostic nomogram was developed based on these risk factors. The time-dependent C-indexes (0.65) were greater than those of the AJCC stage model (0.55) during the 12 to 60 months of follow-up. The calibration plots of the competing risk nomograms demonstrated excellent consistency between actual survival and nomogram predictions. ROC analyses showed that the 1-, 3-, and 5-year AUC values in both the training and validation cohorts were all greater than 0.63 and exceeded those of the AJCC stage model. DCA demonstrated the clinical usefulness of the nomogram. Patients were classified into low-, moderate-, and high-risk groups based on the nomogram scores, with the high-risk group showing significantly higher CSM rates after RFA compared to the other two groups. CONCLUSIONS: We identified Grade, AFP, cirrhosis, tumor size, and tumor number as independent risk factors associated with CSM. The competing risk nomogram exhibited high performance in predicting the probability of CSM for HCC patients undergoing RFA.

Attenuated memory impairment and neuroinflammation in Alzheimer's disease by aucubin via the inhibition of ERK-FOS axis.

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.

Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway.

AIMS: To determine the availability and the potential molecular mechanisms underlying the therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD). MATERIALS AND METHODS: This study employed network pharmacology to assess the feasibility of drug treatment of AD. To determine the cognitive status and emotional state of APPswe/PS1dE9 (APP/PS1) mice after the RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, and open field test) were conducted. Immunofluorescence and immunohistochemical staining were utilized to evaluate hippocampal neuronal status and amyloid (Aß) deposition in mice. RNA-seq and transcription factor prediction analyses were performed to explore the potential molecular mechanisms regulating the therapeutic effects of RTA408. Molecular docking was employed to predict the direct drug targets. To validate these molecular mechanisms, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and immunofluorescence analyses were performed in two instrumental cell lines, i.e., mouse hippocampal neuronal cells (HT22) and microglia (BV2). RESULTS: RTA408 was revealed with the capability to reduce Aß plaque deposition and to restore damaged neurons in the hippocampal region of APP/PS1 mice, ultimately leading to an improvement in cognitive function. This beneficial effect was achieved by balancing the STAT3 pathway. Specifically, RTA408 facilitated the activations of both STAT3/OXR1 and NRF2/ARE axes, thereby enhancing the compromised resistance in neurons to oxidative stress. RTA408 inhibited the NFκB/IL6/STAT3 pathway, effectively countering the neuroinflammation triggered by microglial activation. CONCLUSION: RTA408 is revealed with promising potential in the treatment of AD based on preclinical data.

Differential expression of zinc finger CCHC-type superfamily proteins in thyroid carcinoma and their associations with tumor immunity.

BACKGROUND: The zinc-finger CCHC-type (ZCCHC) superfamily proteins are characterized by the shared sequence CX2-CX4-HX4-C and thought to own high affinity to single-stranded nucleic acids, particularly RNAs. In humans, a total of 24 ZCCHC proteins have been annotated in the HUGO Gene Nomenclature Committee (HGNC, https://www.genenames.org/ ) database with most of these members involved in multiple steps of RNA metabolism. Many studies have indicated that the ZCCHC genes play a regulatory role in the development and progression of solid tumors. To date, the expression pattern and prognostic value of ZCCHC factors in thyroid carcinomas have not been reported. METHODS: Bioinformatics analyses on the functions of ZCCHC factors in thyroid carcinoma (THCA) patients were performed based on various databases, i.e., TCGA, GEPIA, Kaplan-Meier Plotter, and TIMER. RESULTS: Compared with normal tissues, the expression of ZCCHC12 mRNA was significantly increased in THCA tissues. And it was associated with the overall survival of THCA patients, based on the Kaplan-Meier Plotter database. Furthermore, the expression levels of all ZCCHCs were correlated with tumor stages, implying its high relevance to THCA, specifically its immunity. CONCLUSION: The ZCCHC genes, represented by ZCCHC12, are differentially expressed in THCA staging. These genes are associated with immune infiltration of THCA and identified as the potential therapeutic targets for immunotherapy in THCA patients, which are possible novel biomarkers for the treatment of THCA.

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.

Tough Gelatin Hydrogel for Tissue Engineering.

Tough hydrogel has attracted considerable interest in various fields, however, due to poor biocompatibility, nondegradation, and pronounced compositional differences from natural tissues, it is difficult to be used for tissue regeneration. Here, a gelatin-based tough hydrogel (GBTH) is proposed to fill this gap. Inspired by human exercise to improve muscle strength, the synergistic effect is utilized to generate highly functional crystalline domains for resisting crack propagation. The GBTH exhibits excellent tensile strength of 6.67 MPa (145-fold that after untreated gelation). Furthermore, it is directly sutured to a ruptured tendon of adult rabbits due to its pronounced toughness and biocompatibility, self-degradability in vivo, and similarity to natural tissue components. Ruptured tendons can compensate for mechanotransduction by GBTH and stimulate tendon differentiation to quickly return to the initial state, that is, within eight weeks. This strategy provides a new avenue for preparation of highly biocompatible tough hydrogel for tissue regeneration.

Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. MATERIALS AND METHODS: The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. RESULTS: A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aß-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. CONCLUSION: The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.

Molecular mechanisms and clinical applications of exosomes in prostate cancer.

Prostate cancer (PC) is a common tumor in men, and the incidence rate is high worldwide. Exosomes are nanosized vesicles released by all types of cells into multiple biological fluid types. These vesicles contribute to intercellular communication by delivering both nucleic acids and proteins to recipient cells. In recent years, many studies have explored the mechanisms by which exosomes mediate the epithelial-mesenchymal transition, angiogenesis, tumor microenvironment establishment, and drug resistance acquisition in PC, and the mechanisms that have been identified and the molecules involved have provided new perspectives for the possible discovery of novel diagnostic markers in PC. Furthermore, the excellent biophysical properties of exosomes, such as their high stability, high biocompatibility and ability to cross biological barriers, have made exosomes promising candidates for use in novel targeted drug delivery system development. In this review, we summarize the roles of exosomes in the growth and signal transmission in PC and show the promising future of exosome contributions to PC diagnostics and treatment.

MicroRNA-22-3p ameliorates Alzheimer's disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus.

BACKGROUND: Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer's disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. METHODS: The ameliorating effect of miR-22-3p on apoptosis of the Aß-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. RESULTS: The miR-22-3p played an important role in ameliorating apoptosis in the Aß-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aß deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. CONCLUSION: Our study showed that miR-22-3p could improve apoptosis and reduce Aß deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.

A systematic review and meta-analysis on the efficacy and safety of transcatheter arterial chemoembolization combined with radiofrequency ablation in the treatment of primary liver cancer.

Background: Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) intervention in prolonging the long-term survival and prognosis of patients with liver cancer are still controversy compared with the traditional interventional therapy of RFA alone. This meta-analysis aimed to compare the efficacy and safety of combination therapy versus RFA alone. Methods: The related articles were searched in PubMed, Embase, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Science and Technology Journal Database, and China Biomedical Literature Database (CBM). The Chinese and English search keywords included transcatheter arterial chemoembolization, TACE, radiofrequency ablation, RFA, primary liver cancer, and liver tumor. The five evaluation criteria of randomized controlled trials (RCTs) in Cochrane RoB 2.0 repeatedly independently evaluated the bias risks involved in the study and cross-checked the results. Results: A total of 7 articles were included, and the results of bias risk assessment show that 6 articles described the generation of random sequences in detail; There were 3 articles describing allocation concealment in detail; Operator blindness was used in 4 articles; The outcome indicators of 7 documents were complete. The 3-year overall survival rate of the RFA combined with TACE group was significantly better than that of the RFA group [odds ratio (OR) =1.97, 95% confidence interval (CI): 1.42-2.74, Z=4.05, P<0.0001]. The 1-year and 3-year tumor recurrence-free survival rates in the RFA combined with TACE group were significantly better than those in the RFA group (OR =1.88, 95% CI: 1.28-2.76, Z=3.23, P=0.001; OR =2.11, 95% CI: 1.37-3.24, Z=3.38, P=0.0007). There was no significant difference in the complication rate of patients with primary liver cancer between the RFA combined with TACE group and the RFA group (OR =0.79, 95% CI: 0.45-1.39, Z=0.81, P=0.42). Discussion: Meta-analysis results confirmed that TACE combined with RFA was safe and effective in the treatment of primary liver cancer, and can improve the overall survival and recurrence-free survival of patients with primary liver cancer.

Key gene network related to primary ciliary dyskinesia in hippocampus of patients with Alzheimer's disease revealed by weighted gene co-expression network analysis.

BACKGROUND: Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main brain regions involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little is known about its association with primary ciliary dyskinesia (PCD). MATERIAL AND METHODS: The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network. RESULTS: Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients. CONCLUSION: Our study demonstrated that AD and PCD have common metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD. SUBJECTS: Bioinformatics, Cell Biology, Molecular Biology, Neurology.

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b.

The advanced grade glioblastomas are characterized by dismal five-year survival rates and are associated with worse outcomes. Additionally, resistance to therapies is an additional burden responsible for glioma associated mortality. We studied the resistance against temozolomide (TMZ) as a surrogate to understand the mechanism of therapy resistance in glioma cancer cells. Screening of three glioma cells lines, A172, LN229 and SF268 revealed that SF268 glioma cells were particularly resistant to TMZ with the IC-50 of this cell line for TMZ ten times higher than for the other two cell lines. A role of lncRNAs in glioma progression has been identified in recent years and, therefore, we focused on lncRNAs for their role in regulating TMZ resistance in glioma cancer cells. lncRNA HOTTIP was found to be particularly elevated in SF268 cells and over-expression of HOTTIP in both A172 and LN229 remarkably increased their TMZ IC-50s, along with increased cell proliferation, migration, clonogenicity and markers of angiogenesis and metastasis. As a mechanism we observed increased expression of miRNA-10b and mesenchymal markers Zeb1/Zeb2 and reduced expression of E-cadherin in SF268 cells indicating a role of EMT in TMZ resistance. A172 and LN229 cells with overexpressed HOTTIP also had similarly induced EMT and the elevated miR-10b levels. Further, silencing of miR-10b in HOTTIP overexpressing cells as well as the SF268 cells reversed EMT with associated sensitization of all the tested cells to TMZ. Our results thus present a case for HOTTIP in native as well as acquired resistance of glioma cells against chemotherapy, with a key mechanistic role of EMT and the miR-10b. Thus, HOTTIP as well as miR-10b are critical targets for glioma therapy, and need to be tested further.

Targeting long non-coding RNA PVT1/TGF-ß/Smad by p53 prevents glioma progression.

Glioma is a primary intracranial malignant tumor with poor prognosis, and its pathogenesis is unclear. This study discussed the impact of p53/lncRNA plasmacytoma variant translocation 1 (lncRNA PVT1)/transforming growth factor beta (TGF-ß)/Smad axis on the biological characteristics of glioma. Glioma and normal tissues were collected, in which relative lncRNA PVT1 and p53 expression was assessed. Pearson's analysis was adopted for the correlation analysis between lncRNA PVT1 and p53. Short interfering RNA (siRNA) against lncRNA PVT1 (siRNA-PVT1), siRNA-p53 or both was transfected into the glioma cells to evaluate effects of lncRNA PVT1 and p53 on cell proliferation, migration, invasion, and apoptosis. Mouse xenograft model of glioma was established to verify function of lncRNA PVT1 and p53 in vivo. Relationship among p53, lncRNA PVT1 and TGF-ß/Smad was predicted and confirmed. Glioma tissues and cells showed downregulated p53 expression and increased lncRNA PVT1 expression. An adverse relationship was noted between p53 expression and lncRNA PVT1 expression. p53 was shown to be enriched in the lncRNA PVT1 promoter region and resulted in its suppression. p53 inhibited glioma cell proliferation, migration, and invasion, and induced apoptosis as well as arrested tumor growth by downregulating lncRNA PVT1. LncRNA PVT1was found to bind to TGF-ß and activate TGF-ß/Smad pathway, promoting progression of glioma. Consequently, p53 exerts anti-oncogenic function on glioma development by suppressing lncRNA PVT1 and subsequently inactivating TGF-ß/Smad pathway.

LncRNA FOXD3-AS1 Promotes Tumorigenesis of Glioma via Targeting miR-128-3p/SZRD1 Axis.

BACKGROUND: The aim of the current study was to investigate the roles of LncRNA FOXD3-AS1 (FOXD3-AS1) in the glioma progression, and its underlying mechanism of competing endogenous RNA (ceRNA) network of FOXD3-AS1/miR-128-3p/SZRD1. MATERIALS AND METHODS: The FOXD3-AS1 expression and its prognostic relation were detected by bioinformatics tool. Next, glioma cell lines (HS683, U251, T98G, and SNB-19) were used to verify the FOXD3-AS1 expression. Furthermore, the roles of the FOXD3-AS1/miR-128-3p/SZRD1 axis on the glioma development in vitro and in vivo were examined. RESULTS: Bioinformatics analysis showed that FOXD3-AS1 was upregulated in the glioma and linked with poor prognosis. Consistently, FOXD3-AS1 level was overexpressed in the glioma cell lines (HS683 and U251). Subsequently, we verified that silencing of FOXD3-AS1 (si-FOXD3-AS1) restrained the cell proliferation, invasion, and tumor growth in vivo, and induced G0/G1 arrest, and promoted apoptosis. Further study also stated that FOXD3-AS1 interacted with miR-128-3p and SZRD1 was the target gene of miR-128-3p. Moreover, overexpression of miR-128-3p restrained the cell proliferation and metastasis of glioma, and reduced the SZRD1 level. Rescue assay illustrated that miR-128-3p inhibitor could reverse the suppressive impact of si-FOXD3-AS1 on the glioma progression. Similarly, SZRD1 overexpression could neutralize the influences of miR-128-3p mimic on glioma progression. CONCLUSION: FOXD3-AS1 promoted the tumorigenesis of glioma, and exerted its function to modulate SZRD1 by targeting miR-128-3p.

Beyond the virus: a first look at coronavirus-themed Android malware.

As the COVID-19 pandemic emerged in early 2020, a number of malicious actors have started capitalizing the topic. Although a few media reports mentioned the existence of coronavirus-themed mobile malware, the research community lacks the understanding of the landscape of the coronavirus-themed mobile malware. In this paper, we present the first systematic study of coronavirus-themed Android malware. We first make efforts to create a daily growing COVID-19 themed mobile app dataset, which contains 4,322 COVID-19 themed apk samples (2,500 unique apps) and 611 potential malware samples (370 unique malicious apps) by the time of mid-November, 2020. We then present an analysis of them from multiple perspectives including trends and statistics, installation methods, malicious behaviors and malicious actors behind them. We observe that the COVID-19 themed apps as well as malicious ones began to flourish almost as soon as the pandemic broke out worldwide. Most malicious apps are camouflaged as benign apps using the same app identifiers (e.g., app name, package name and app icon). Their main purposes are either stealing users' private information or making profit by using tricks like phishing and extortion. Furthermore, only a quarter of the COVID-19 malware creators are habitual developers who have been active for a long time, while 75% of them are newcomers in this pandemic. The malicious developers are mainly located in the US, mostly targeting countries including English-speaking countries, China, Arabic countries and Europe. To facilitate future research, we have publicly released all the well-labelled COVID-19 themed apps (and malware) to the research community. Till now, over 30 research institutes around the world have requested our dataset for COVID-19 themed research.