GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Genistein alleviates dextran sulfate sodium-induced colitis in mice through modulation of intestinal microbiota and macrophage polarization.

OBJECTIVES: Ulcerative colitis (UC) is a colonic immune system disorder, manifested with long duration and easy relapse. Genistein has been reported to possess various biological activities. However, it remains unclear whether genistein can ameliorate UC by modulating the homeostasis of the intestinal bacterial community. METHODS: The dextran sodium sulfate (DSS)-induced UC mice were administrated with genistein (20 mg/kg/day) or genistein (40 mg/kg/day) for ten days. The general physical condition of the mice was monitored. After sacrifice, the changes in colon length and colonic pathological morphology were observed. The expression of intestinal barrier proteins, inflammatory cytokines, and macrophage markers in the colon was detected. The composition and metabolic products of the intestinal microbiota were analyzed. RESULTS: Genistein treatment visibly improved body weight change and disease activity index in DSS-induced mice. Genistein treatment ameliorated colonic pathological alterations and promoted the expression of mucin-2 and tight junction proteins. Genistein administration inhibited myeloperoxidase activity and colonic inflammatory cytokines. Furthermore, genistein administration improved the structure of the intestinal microbial community, promoted the production of short-chain fatty acids, and modulated macrophage polarization. CONCLUSIONS: These results revealed that genistein mediated macrophage polarization balance by improving intestinal microbiota and its metabolites, thereby alleviating DSS-induced colitis.

ML365 ameliorates postoperative cognitive impairment in aged mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1ß expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1ß expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

Compliant Grasping Control for a Tactile Self-Sensing Soft Gripper.

Soft grippers with good passive compliance can effectively adapt to the shape of a target object and have better safe grasping performance than rigid grippers. However, for soft or fragile objects, passive compliance is insufficient to prevent grippers from crushing the target. Thus, to complete nondestructive grasping tasks, precision force sensing and control are immensely important for soft grippers. In this article, we proposed an online learning self-tuning nonlinearity impedance controller for a tactile self-sensing two-finger soft gripper so that its grasping force can be controlled accurately. For the soft gripper, its grasping force is sensed by a liquid lens-based optical tactile sensing unit that contains a self-sensing fingertip and a liquid lens module and has many advantages of a rapid response time (about 0.04 s), stable output, good sensitivity (>0.4985 V/N), resolution (0.03 N), linearity (R2 > 0.96), and low cost (power consumption: 5 mW, preparation cost

Discriminative and Robust Autoencoders for Unsupervised Feature Selection.

Many recent research works on unsupervised feature selection (UFS) have focused on how to exploit autoencoders (AEs) to seek informative features. However, existing methods typically employ the squared error to estimate the data reconstruction, which amplifies the negative effect of outliers and can lead to performance degradation. Moreover, traditional AEs aim to extract latent features that capture intrinsic information of the data for accurate data recovery. Without incorporating explicit cluster structure-detecting objectives into the training criterion, AEs fail to capture the latent cluster structure of the data which is essential for identifying discriminative features. Thus, the selected features lack strong discriminative power. To address the issues, we propose to jointly perform robust feature selection and k -means clustering in a unified framework. Concretely, we exploit an AE with a l2,1 -norm as a basic model to seek informative features. To improve robustness against outliers, we introduce an adaptive weight vector for the data reconstruction terms of AE, which assigns smaller weights to the data with larger errors to automatically reduce the influence of the outliers, and larger weights to the data with smaller errors to strengthen the influence of clean data. To enhance the discriminative power of the selected features, we incorporate k -means clustering into the representation learning of the AE. This allows the AE to continually explore cluster structure information, which can be used to discover more discriminative features. Then, we also present an efficient approach to solve the objective of the corresponding problem. Extensive experiments on various benchmark datasets are provided, which clearly demonstrate that the proposed method outperforms state-of-the-art methods.

FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma.

Glioma is the most common primary brain tumor. Filamin-binding LIM protein 1 (FBLIM1) has been identified in multiple cancers and is suspected of playing a part in the development of tumors. However, the potential function of FBLIM1 mRNA in glioma has not been investigated. In this study, the clinical information and transcriptome data of glioma patients were, respectively, retrieved from the TCGA and CGGA databases. The expression level of FBLIM1 mRNA was shown to be aberrant in a wide variety of malignancies. Significantly, when glioma samples were compared to normal brain samples, FBLIM1 expression was shown to be significantly elevated in the former. A poor prognosis was related to high FBLIM1 expression, which was linked to more advanced clinical stages. Notably, multivariate analyses demonstrated that FBLIM1 expression was an independent predictor for the overall survival of glioma patients. Immune infiltration analysis disclosed that FBLIM1 expression had relevance with many immune cells. The results of RT-PCR suggested that FBLIM1 expression was markedly elevated in glioma specimens. Functional experiments unveiled that the knockdown of FBLIM1 mRNA suppressed glioma cell proliferation. In general, we initially discovered that FBLIM1 mRNA might be a possible prognostic marker in glioma.

Experimental study on a -86 °C cascade refrigeration unit with environmental-friendly refrigerants R290-R170.

Ultralow-temperature refrigeration faces significant issues linked to the security of the cold chain for the production, storage, transportation, and distribution of COVID-19 vaccines. The use of environmentally friendly refrigerants in cascade refrigeration systems (CRS) to provide low-temperature range is motivated by the high demand for ultralow-temperature refrigeration units. In the current study, a CRS is built to generate a low temperature of -86 °C for the storage of COVID-19 vaccines. In the CRS, the natural refrigerant combination R290-R170 is used as high-temperature and low-temperature fluids. The pull-down performance of the -86 °C freezer is explored experimentally, and the stable operating performance is determined at two different dry bulb and wet bulb temperatures. Various status monitors are set up to analyze the CRS's operation features, and several temperature monitors are put in the freezer to analyze temperature variations. The power consumption of the CRS is examined and evaluated. Finally, several key findings are summarized. The current work is the first to involve experimental measurements on -86 °C temperature generated by a CRS, which can substantially enhance experiment data in ultralow-temperature refrigeration and contribute to a more in-depth understanding of the operation performance of a -86 °C ultralow-temperature freezer.

[miR-497 inhibits the growth and metastasis of SGC-7901 human gastric cancer anoikis resistant cells via blocking Wnt/ß-catenin signaling pathway].

Objective To investigate the effects of microRNA497 (miR-497) on the metastasis of gastric cancer and its possible molecular mechanism. Methods SGC-7901 gastric cancer parent cells were cultured in an ultra-low adhesion environment, and the anoikis resistance model of SGC-7901 cells was created after re-adhesion. Clone formation assay, flow cytometry, TranswellTM test and scratch healing test were used to detect the differences of biological behavior compared with their parent cells. Fluorescence quantitative PCR was performed to detect the expression of miR-497. Western blot analysis was used to detect the changes of key proteins of Wnt/ß-catenin signaling pathway and epithelial mesenchymal transformation (EMT) related proteins such as vimentin and E-cadherin. Parent cells and anoikis resistant SGC-7901 cells were transfected with miR-497 inhibitor or miR-497 mimic, and CCK-8 assay was used to detect the proliferation activity. TranswellTM invasion assay was performed to detect the invasion ability of cells. TranswellTM migration test and scratch healing assay was used to determine the migration ability. Western blot analysis was used to detect the expressions of Wnt1, ß-catenin, vimentin and E-cadherin. By transfecting miR-497 mimic into the anoikis resistance SGC-7901 cells and inoculating them subcutaneously in nude mice, the changes in the volume and mass of tumor tissues were measured and recorded. Western blot analysis was used to determine the expressions of Wnt1, ß-catenin, vimentin and E-cadherin of tumor tissues. Results Compared with the parent cells, the anoikis resistance SGC-7901 gastric cancer cells had faster proliferation rate, stronger colony formation, lower apoptosis rate, stronger invasion and migration ability. The expression of miR-497 was significantly decreased. After down-regulation of miR-497, the proliferation ability, invasion and migration ability were significantly enhanced. The expressions of Wnt1, ß-catenin and vimentin increased significantly, while E-cadherin decreased notably. The results of up-regulation miR-497 were the opposite. The tumor growth rate, tumor volume and mass of miR-497 overexpression group were significantly lower than those of control group. The expressions of Wnt1, ß-catenin and vimentin decreased significantly, while the expression of E-cadherin increased significantly. Conclusion The expression of miR-497 is low in the anoikis resistance SGC-7901 cells. miR-497 can inhibit the growth and metastasis of gastric cancer cells by blocking Wnt/ß-catenin signaling pathway and EMT.

JFD, a Novel Natural Inhibitor of Keap1 Alkylation, Suppresses Intracellular Mycobacterium Tuberculosis Growth through Keap1/Nrf2/SOD2-Mediated ROS Accumulation.

It is an effective strategy to treat tuberculosis by enhancing reactive oxygen species- (ROS-) mediated killing of Mycobacterium tuberculosis in macrophages, but there are no current therapeutic agents targeting this pathway. Honeysuckle has been used as the traditional medicine for tuberculosis treatment for 1500 years. Japoflavone D (JFD) is a novel biflavonoid isolated from Honeysuckle promoting ROS accumulation by Nrf2 pathway in hepatocarcinoma cells. However, its activity to kill M. tuberculosis in macrophages and molecular mechanism has not been reported. Our results showed that JFD enhances the M. tuberculosis elimination by boosting ROS levels in THP-1 cells. Moreover, the massive ROS accumulation activates p38 to induce apoptosis. Notably, the mechanism revealed that JFD suppresses the nuclear transport of Nrf2, thereby inhibiting SOD2 transcription, leading to a large ROS accumulation. Further studies showed that JFD disrupts the Keap1 alkylation at specific residues Cys14, Cys257, and Cys319, which is crucial for Nrf2 activation, thereby interrupts the nuclear transport of Nrf2. In pharmacokinetic study, JFD can stay as the prototype for 24 h in mice and can be excreted in feces without any toxicity. Our data reveal for the first time that a novel biflavonoid JFD as a potent inhibitor of Keap1 alkylation can suppress the nuclear transport of Nrf2. And it is the first research of the inhibitor of Keap1 alkylation. Furthermore, JFD robustly promotes M. tuberculosis elimination from macrophages by inhibiting Keap1/Nrf2/SOD2 pathway, resulting in the ROS accumulation. This work identified Keap1 alkylation as a new drug target for tuberculosis and provides a preliminary basis for the development of antituberculosis lead compounds based on JFD.

New Approach for Targeted Treatment of Mild COVID-19 by Honeysuckle through Network Pharmacology Analysis.

OBJECTIVE: To investigate the potential pharmacological value of extracts from honeysuckle on patients with mild coronavirus disease 2019 (COVID-19) infection. METHODS: The active components and targets of honeysuckle were screened by Traditional Chinese Medicine Database and Analysis Platform (TCMSP). SwissADME and pkCSM databases predict pharmacokinetics of ingredients. The Gene Expression Omnibus (GEO) database collected transcriptome data for mild COVID-19. Data quality control, differentially expressed gene (DEG) identification, enrichment analysis, and correlation analysis were implemented by R toolkit. CIBERSORT evaluated the infiltration of 22 immune cells. RESULTS: The seven active ingredients of honeysuckle had good oral absorption and medicinal properties. Both the active ingredient targets of honeysuckle and differentially expressed genes of mild COVID-19 were significantly enriched in immune signaling pathways. There were five overlapping immunosignature genes, among which RELA and MAP3K7 expressions were statistically significant (P < 0.05). Finally, immune cell infiltration and correlation analysis showed that RELA, MAP3K7, and natural killer (NK) cell are with highly positive correlation and highly negatively correlated with hematopoietic stem cells. CONCLUSION: Our analysis suggested that honeysuckle extract had a safe and effective protective effect against mild COVID-19 by regulating a complex molecular network. The main mechanism was related to the proportion of infiltration between NK cells and hematopoietic stem cells.

FASN Knockdown Inhibited Anoikis Resistance of Gastric Cancer Cells via P-ERK1/2/Bcl-xL Pathway.

Anoikis resistance (AR) is a crucial step in tumor metastasis. The overexpression of fatty acid synthase (FASN) is not only related to the AR of osteosarcoma cells, but also evidenced on gastric cancer (GC). This study investigated the role of FASN in the AR of GC cells. Plates coated with poly-HEMA were used for the culture of cells with AR. Small interfering RNA targeting FASN (siFASN) was transfected into MNK-45 and AGS cells. The number and apoptosis of cells were assessed by a hemacytometer and Annexin-V-FITC/PI assay, respectively. Aggregated cells and colony numbers were manually counted under a microscope. The migration and invasion rates were measured via wound healing and Transwell invasion assays, respectively. The levels of FASN, phosphorylated (p)-ERK1/2, ERK1/2 and Bcl-xL were detected through western blot or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results showed that the cell numbers of MNK-45 and AGS were increased while that of GES-1 cell was decreased during the culture in suspension. A higher apoptosis rate and a smaller number of aggregated cells were observed in GES-1 cells in comparison with MNK-45 and AGS cells. A larger colony number, greater migration and invasion rates, and higher mRNA and protein expressions of FASN were presented in the AR group compared with the control group. Cells transfected with siFASN possessed lower migration and invasion rates, reduced expressions of FASN mRNA and protein, p-ERK1/2 and Bcl-xL, and induced a significantly declined ratio of p-ERK1/2 to ERK1/2. These findings suggest that down-regulation of FASN suppresses the AR of GC cells, which may be related to the inhibition of p-ERK1/2/Bcl-xL pathway.

Safety and effectiveness of SARS-CoV-2 vaccines: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness and safety of the SARS-CoV-2 vaccines currently undergoing clinical trials. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched to collect open human COVID-19 vaccines randomized controlled trials, without limiting the search time and language. The research papers collected in the above-mentioned databases were initially screened according to the title and abstract content and merged, and the repeated ones were removed. After reading the full text of the remaining research, the studies that did not meet the inclusion criteria were excluded, and finally, nine studies were obtained. After extracting the statistical data of adverse events in the study, load them into Review Manager for heterogeneity analysis. RESULTS: The incidence of adverse reactions of inactivated virus vaccines, RNA vaccines, and adenovirus vector vaccines was higher than that of placebo. Common adverse reactions included pain, swelling, and fever at the injection site. CONCLUSION: From the perspective of effectiveness, RNA vaccine > adenovirus vector vaccine > inactivated virus vaccine. From the perspective of safety, the incidence of adverse reactions of the three vaccines is higher than that of a placebo, and the incidence of adverse reactions of the adenovirus vector vaccine is higher.

PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation.

Organ transplantation has been employed upon serious injuries, but a T-cell-mediated potent inflammatory immune response often leads to graft rejection. Immunosuppressive drugs such as rapamycin (RAPA) have to be taken after organ transplantation, but long-term use of these drugs causes severe adverse effects. Immune checkpoint pathways such as the programmed death-receptor 1/programmed death-ligand 1 (PD-1/PD-L1) provides an immunosuppressive environment, preventing excessive tissue destruction due to inflammatory immune responses. In this study, we bioengineered cell membrane-derived PD-L1 nanovesicles (PD-L1 NVs) to carry low doses of RAPA. These NVs inhibited T-cell activation and proliferation in vitro, by enhancing the PD-1/PD-L1 immune co-inhibitory signaling axis and inhibiting the mTOR pathway. Importantly, PD-L1 NVs encapsulated with rapamycin exerted stronger effects on inhibiting T-cell proliferation than PD-L1 NVs or rapamycin alone. This can be recapitulated in a mouse skin transplantation model, leading to the weakened alloimmune response and allograft tolerance. We also found that PD-L1/rapamycin vesicles have additional function to induce regulatory T cells in the recipient spleens. Our study highlighted the power of combining low-dose rapamycin and PD-L1 in the nanovesicles as immunosuppressants to promote allograft acceptance.

Design of Stretchable Holey Gold Biosensing Electrode for Real-Time Cell Monitoring.

In bioelectronics, gold thin films have been widely used as sensing electrodes for probing biological events due to their high conductivity, chemical inertness, biocompatibility, wide electrochemical window, and facile surface modification. However, they are intrinsically not stretchable, which limits their applications in detecting biological reactions when a soft biological system is mechanically deformed. Here, we report on a nanosphere lithography-based strategy to generate ordered microhole gold thin-film electrodes supported by elastomeric substrates. Both experimental and theoretical studies show that the presence of microholes substantially suppresses the catastrophic crack propagation-the main reason for electrical failure for a continuous gold film. As a result, the holey gold film achieves a ∼94% stretchable limit, after which the conductivity is lost, in contrast to ∼4% for the nonstructured counterpart. Furthermore, the pinhole gold electrode is successfully used to monitor the H2O2 released from living cells under dynamic stretching conditions.

Effects of regulating miR-132 mediated GSK-3ß on learning and memory function in mice.

The aimf of this study was to explore effects of miR-132 and glycogen synthase kinase-3ß (GSK-3ß) on learning and memory in mice. miR-132 inhibitor GSK-3ß overexpression agent (sh-GSK-3ß) and normal saline (negative control group) were injected into the hippocampus of adult mice, and healthy adult mice were taken as the unrelated control group. The expression of miR-132 and GSK-3ß in the hippocampus of adult and elderly mice was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Morris water maze test was employed to detect learning and memory function in mice. The dual luciferase reporter was adopted to determine the relationship between miR-132 and GSK-3ß. Compared with the adult group, the expression of miR-132 was significantly downregulated in the hippocampus in the elderly group, while the expression of GSK-3ß was upregulated. Injecting miR-132 inhibitor into the hippocampus of adult mice led to a significant increase in escape latency and a significant decrease in the number of times of crossing platforms. The injection of GSK-3ß overexpression agent into the hippocampus of adult mice resulted in a marked increase in escape latency and a significant decrease in the number of times of crossing platforms in the water maze test. It was also found that downregulation of GSK-3ß reversed the decline in learning and memory in mice caused by downregulation of miR-132 expression. The dual luciferase report identified a targeted regulatory relationship between miR-132 and GSK-3ß. Overexpression of miR-132 can inhibit the expression of GSK-3ß in mouse learning and memory ability, which provides some inspiration for understanding the occurrence of learning and memory disorders and future treatment methods.

Tissue Inhibitor of Matrix Metalloproteinase 2-Loaded Polylactic Acid-Polyethylene Glycol Nanoparticles Directly Regulates Renal Tubular Epithelial Cell Proliferation via Protein Tyrosine Kinase KIT.

TIMP2 has been previously reported to be associated with acute kidney injury (AKI); however, the underlying mechanism remains unclear. Therefore, the present study investigated the regulation of TIMP2 in human tubular epithelial cells HK-2 cells. Proliferation of HK-2 cells treated by TIMP2 at normal expression level was detected. GST pulldown and mass spectrometry were performed to investigate the interacting protein of TIMP2 and immunofluorescence test was used to determine the location of the protein in HK-2 cells. Cell viability as well as the expression level of CCND1, C-FOS, MAPK1 and P-MAPK1 were detected in the samples treated by overexpressed TIMP2 and the inhibitor of the interacting protein KIT. TIMP2 significantly inhibited cell proliferation compared with the control and BB-94-treated groups (P < 0.05). KIT was identified as the interacting protein of TIMP2, and was located in both the cytoplasm and membrane of HK-2 cells. Inhibited KIT and the overexpressed of TIMP2 both significantly suppressed cell proliferation and decreased the expression levels of CCND1, MAPK1, and P-MAPK1 compared with the control (P < 0.05). No significant difference was observed in cell proliferation and the expression level of aforementioned proteins between overexpressed TIMP2 and KIT-inhibited group. The results revealed that TIMP2 regulates cell proliferation by reducing the expression levels of CCND1, MAPK1, and P-MAPK1 via KIT, indicating that TIMP2 directly regulates cell proliferation without inhibiting matrix metalloproteinases in AKI. Furthermore, PLA-PEG nanoparticles successfully transported TIMP2 to the target with no significant effect on cell proliferation.

Bioinformatic Analysis of Differentially Expressed Genes and Screening of Hub Genes in Uveal Melanoma Cells with BRCA1-Associated Protein 1 Related Protein 1 Depletion.

Recent studies have found that chromosome 3 is frequently mutated in metastatic uveal melanoma (UVM), which leads to the loss of BAP1 expression or the weakening of BRCA1-associated protein 1 (BAP1) function and promotes metastasis of uveal melanoma cells. However, the specific signaling pathways that are affected by BAP1 depletion in uveal melanoma remain unclear. Our aim in this study was to verify the effect and regulatory mechanism of BAP1 on uveal melanoma. RT-qPCR and western blotting results showed that BAP1 was significantly down-regulated in OCM-1A cells treated with a BAP1 shRNA vector. MTT, cell scratch and transwell migration assays showed that low expression of BAP1 significantly promoted the proliferation and migration of UVM cells. A total of 269 up-regulated and 807 down-regulated genes were identified from the combined GSE110193 and GSE48863 data sets. These differentially expressed genes are mainly involved in the composition of extracellular matrix and the regulation of the Wnt signaling pathway and are closely related to the cell adhesion pathway. CXCL8, COL5A3, COL11A1, and COL12A1 were among the differentially expressed genes and are closely related to the prognosis of UVM. Therefore, the deletion of BAP1 is closely related to poor prognosis of UVM and is a risk factor for UVM metastasis. The potential targets of BAP1 include CXCL8, COL5A3, COL11A1, and COL12A1. It is believed that BAP1 regulates UVM cell adhesion through these four genes and ultimately regulates tumor development and migration.

Evaluation of Different Blood Circulating miRNAs for Hepatocellular Carcinoma Diagnosis.

The current study was conducted to investigate the potential of three circulating miRNAs (miR-21, miR-16 and miR-100) as HCC diagnostic marker in the population living in Guangdong province, China. First, the Fe3O4 and Fe3O4@SiO2 magnetic microsphere were prepared. Fe3O4@SiO2 microspheres were further used for total RNA purification from serum. After that, the real-time qPCR was conducted for the detecting the miRNA in the serum of HCC patients and healthy volunteers. Scanning electron microscope and transmission electron microscope images showed that monodisperse Fe3O4 and Fe3O4@SiO2 microspheres were successfully synthesized with a mean diameter of about 500 nm and 600 nm, respectively. The microsphere was spherical in shape with good state of dispersion. The characteristic peak at 1088.8 cm-1 in FTIR spectra belonged to the asymmetry stretching vibration of Si-O-Si, which confirmed the SiO2 coating on Fe3O4 microspheres. The successful amplification of miRNAs in qPCR verified that the total RNA extracted using the Fe3O4@SiO2 microspheres retained high quality. The real time PCR results showed that miR-21 was differentially expressed in the serum of HCC patients and healthy volunteers. miR-21 and alpha-fetoprotein (AFP) together could be potentially used as HCC diagnostic marker in Guangdong province population in China.

Disruptive, Soft, Wearable Sensors.

The wearable industry is on the rise, with a myriad of technical applications ranging from real-time health monitoring, the Internet of Things, and robotics, to name but a few. However, there is a saying "wearable is not wearable" because the current market-available wearable sensors are largely bulky and rigid, leading to uncomfortable wearing experience, motion artefacts, and poor data accuracy. This has aroused a world-wide intensive research quest for novel materials, with the aim of fabricating next-generation ultra-lightweight and soft wearable devices. Such disruptive second-skin-like biosensing technologies may enable a paradigm shift from current wearable 1.0 to future wearable 2.0 products. Here, the state-of-the-art progress made in the key phases for future wearable technology, namely, wear → sense → communicate → analyze → interpret → decide, is summarized. Without a doubt, materials innovation is the key, which is the main focus of the discussion. In addition, emphasis is also given to wearable energy, multicomponent integration, and wireless communication.