A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

BACKGROUND: The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM. METHODS: We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People's Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4. RESULTS: BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4. CONCLUSIONS: BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.

Palladium-catalyzed [4 + 2] cycloaddition of 2-methylidenetrimethylene carbonate or methylene cyclic carbamate with sulfamate-derived cyclic imines.

A palladium-catalyzed [4 + 2] cycloaddition of 2-methylidenetrimethylene carbonate or methylene cyclic carbamate with sulfamate-derived cyclic imines has been successfully developed under mild reaction conditions, affording pharmacologically interesting oxazine or hydropyrimidine derivatives in high yields (up to 99% yield). Furthermore, the cycloaddition reactions could be efficiently scaled up and several synthetic transformations were accomplished for the construction of other useful 1,3-oxazine and hydropyrimidinone derivatives.

Design, synthesis and bioactivity evaluation of selenium-containing PI3Kδ inhibitors.

PI3Kδ inhibitors play an important role in the treatment of leukemia, lymphoma and autoimmune diseases. Herein, using our reported compounds as the lead compound, we designed and synthesized a series of selenium-containing PI3Kδ inhibitors based on quinazoline and pyrido[3,2-d]pyrimidine skeletons. Among them, compound Se15 showed sub-nanomolar inhibition against PI3Kδ and strong δ-selectivity. Moreover, Se15 showed potent anti-proliferative effect on SU-DHL-6 cells with an IC50 value of 0.16 µM. Molecular docking study showed that Se15 was able to form multiple hydrogen bonds with PI3Kδ and was close proximity and stacking with PI3Kδ selective region. In conclusion, the Se-containing compound Se15 bearing pyrido[3,2-d]pyrimidine scaffold is a novel potent and selective PI3Kδ inhibitor. The introduction of selenium can enrich the structure of PI3Kδ inhibitors and provide a new idea for design of novel PI3Kδ inhibitors.

Biomimetic nanoparticles to enhance the reverse cholesterol transport for selectively inhibiting development into foam cell in atherosclerosis.

A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion "recruitment" properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized "homing" target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized ß-cyclodextrin (ß-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.

Transient, Implantable, Ultrathin Biofuel Cells Enabled by Laser-Induced Graphene and Gold Nanoparticles Composite.

Transient power sources with excellent biocompatibility and bioresorablility have attracted significant attention. Here, we report high-performance, transient glucose enzymatic biofuel cells (TEBFCs) based on the laser-induced graphene (LIG)/gold nanoparticles (Au NPs) composite electrodes. Such LIG electrodes can be easily fabricated from polyimide (PI) with an infrared CO2 laser and exhibit a low impedance (16 Ω). The resulted TEBFC yields a high open circuit potential (OCP) of 0.77 V and a maximum power density of 483.1 µW/cm2. The TEBFC not only exhibits a quick response time that enables reaching the maximum OCP within 1 min but also owns a long lifetime over 28 days in vitro. The excellent biocompatibility and transient performance from in vitro and in vivo tests allow long-term implantation of TEBFCs in rats for energy harvesting. The TEBFCs with advanced processing methods provide a promising power solution for transient electronics.

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

The therapeutic potential of exosomes derived from different cell sources in liver diseases.

Exosomes are small nanovesicles with a size of approximately 40-120 nm that are secreted from cells. They are involved in the regulation of cell homeostasis and mediate intercellular communication. In addition, they carry proteins, nucleic acids, and lipids that regulate the biological activity of receptor cells. Recent studies have shown that exosomes perform important functions in liver diseases. This review will focus on liver diseases (drug-induced liver injury, hepatic ischemia-reperfusion injury, liver fibrosis, acute liver failure, and hepatocellular carcinoma) and summarize the therapeutic potential of exosomes from different cell sources in liver disease.

Physiological adjustment of pomegranate pericarp responding to sunburn and its underlying molecular mechanisms.

BACKGROUND: Sunburn is common in pomegranate, and sunburned fruits have poor appearance and low marketability. However, the physiological and metabolic responses to sunburn and their underlying molecular mechanisms in pomegranate fruit are little understood. Fruit of sunburn-sensitive cultivar 'Hongyushizi' was used to carry out physiological parameter detection and widely-targeted metabolomics and transcriptome study. RESULTS: Malondialdehyde and relative conductivity increased with the severity of sunburn, which indicated increased membrane injury. Meanwhile, the content of antioxidants (total phenols and flavonoids), which reduce and repair membrane damage, increased and were accompanied by increases in total antioxidant capacity. In sunburned fruits compared with controls, 129 metabolites changed (including naringenin, pelargonidin and kaempferol) and 447 differentially expressed genes including CHI (Pgr25966.1), F3'5'H (Pgr26644.1), and CHS (Pgr005566.1) may have contributed to these changes. Transcription factors, such as NAC 5 (Pgr008725.1), MYB 93 (Pgr001791.1), and MYB 111 (Pgr027973.1) may be involved in phenylpropanoid and flavonoid biosynthesis by regulating the CHI, F3'5'H, and CHS etc. CONCLUSIONS: These findings provide insight into the sunburn mechanisms of pomegranate, and also into the genetic improvement of fruit sunburn.

Characterization of the ABC Transporter G Subfamily in Pomegranate and Function Analysis of PgrABCG14.

ATP-binding cassette subfamily G (ABCG) proteins play important roles in plant growth and development by transporting metabolites across cell membranes. To date, the genetic characteristics and potential functions of pomegranate ABCG proteins (PgrABCGs) have remained largely unknown. In this study, we found that 47 PgrABCGs were divided into five groups according to a phylogenetic analysis; groups I, II, III, and IV members are half-size proteins, and group V members are full-size proteins. PgrABCG14, PgrABCG21, and PgrABCG47 were highly expressed in the inner seed coat but had very low expression levels in the outer seed coat, and the expression levels of these three PgrABCG genes in the inner seed coats of hard-seeded pomegranate 'Dabenzi' were higher than those of soft-seeded pomegranate 'Tunisia'. In addition, the expression of these three PgrABCG genes was highly correlated with the expression of genes involved in lignin biosynthesis and hormone signaling pathways. The evolution of PgrABCG14 presents a highly similar trend to the origin and evolution of lignin biosynthesis during land plant evolution. Ectopic expression of PgrABCG14 in Arabidopsis promoted plant growth and lignin accumulation compared to wild type plants; meanwhile, the expression levels of lignin biosynthesis-related genes (CAD5, C4H, and Prx71) and cytokinin response marker genes (ARR5 and ARR15) were significantly upregulated in transgenic plants, which suggests the potential role of PgrABCG14 in promoting plant growth and lignin accumulation. Taken together, these findings not only provide insight into the characteristics and evolution of PgrABCGs, but also shed a light on the potential functions of PgrABCGs in seed hardness development.

A novel hierarchical machine learning model for hospital-acquired venous thromboembolism risk assessment among multiple-departments.

Venous thromboembolism (VTE) is a common vascular disease and potentially fatal complication during hospitalization, and so the early identification of VTE risk is of significant importance. Compared with traditional scale assessments, machine learning methods provide new opportunities for precise early warning of VTE from clinical medical records. This research aimed to propose a two-stage hierarchical machine learning model for VTE risk prediction in patients from multiple departments. First, we built a machine learning prediction model that covered the entire hospital, based on all cohorts and common risk factors. Then, we took the prediction output of the first stage as an initial assessment score and then built specific models for each department. Over the duration of the study, a total of 9213 inpatients, including 1165 VTE-positive samples, were collected from four departments, which were split into developing and test datasets. The proposed model achieved an AUC of 0.879 in the department of oncology, which outperformed the first-stage model (0.730) and the department model (0.787). This was attributed to the fully usage of both the large sample size at the hospital level and variable abundance at the department level. Experimental results show that our model could effectively improve the prediction of hospital-acquired VTE risk before image diagnosis and provide decision support for further nursing and medical intervention.

Pear metal transport protein PbMTP8.1 confers manganese tolerance when expressed in yeast and Arabidopsis thaliana.

Manganese (Mn) is demonstrated to be essential for plants. Ion homeostasis is maintained in plant cells by specialized transporters. PbMTP8.1, which encodes a putative Mn-CDF transporter in Pyrus bretschneideri Rehd, was expressed mainly in leaves and complemented the Mn hypersensitivity of the Mn-sensitive yeast mutant △pmr1 in previous research conducted by our laboratory. In the present study, we report that the expression of PbMTP8.1 can enhance Mn tolerance and accumulation in Saccharomyces cerevisiae. Subcellular localization analysis of the PbMTP8.1-GFP fusion protein indicated that PbMTP8.1 was targeted to the pre-vacuolar compartment (PVC). In addition, the overexpression of PbMTP8.1 in Arabidopsis thaliana conferred increased resistance to plants under toxic Mn levels, as indicated by increased fresh and dry weights of shoots and roots. Mn accumulation in vacuoles of PbMTP8.1-overexpressing plants was significantly increased when compared with that in wild-type plants under Mn stress. This suggests that a considerable proportion of Mn enters into the vacuoles through a PbMTP8.1-dependent mechanism. Taken together, these results indicate PbMTP8.1 is a Mn-specific transporter that is localized to the PVC, and confers Mn tolerance by sequestering Mn into the vacuole.

Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. In in vivo study, male C57BL/6J wild type (WT) and endothelial-specific conditional PPARγ knockout mice were gavage fed with 0.7 g/kg/day ethanol or volume-matched water daily for 8 weeks. From the 7th week, 3 mg/kg/day GW9662 (a selective PPARγ antagonist) was intraperitoneally given for two weeks. Cerebral ischemia/reperfusion (I/R) injury and expression of manganese superoxide dismutase (MnSOD) and adhesion molecules, neutrophil infiltration, and microglial activation in the cerebral cortex before and following a 90 min unilateral middle cerebral artery occlusion (MCAO)/24 h reperfusion were evaluated. In in vitro study, the impact of chronic alcohol exposure on expression of PPARγ and MnSOD in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs) was measured. PPARγ and MnSOD were significantly upregulated in the cerebral cortex of ethanol-fed WT mice and low-concentration ethanol-exposed C57BL/6J MBMVECs. GW9662 significantly inhibited alcohol-induced upregulation of MnSOD. Eight-week ethanol feeding significantly reduced cerebral I/R injury and alleviated the post-ischemic inflammatory response (upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin, microglial activation, and neutrophil infiltration). Treatment with GW9662 and endothelial-specific conditional knockout of PPARγ did not alter cerebral I/R injury and the inflammatory response in the control mice but abolish the neuroprotective effect in ethanol-fed mice. In addition, GW9662 and endothelial-specific conditional knockout of PPARγ diminished the inhibitory effect of LAC on the post-ischemic expression of adhesion molecules and neutrophil infiltration. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing the post-ischemic inflammation via activation of PPARγ.

Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS.

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIαCreERT2/+/L-PGDS+/+, and CaMKIIαCreERT2/+/L-PGDSflox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIαCreERT2/+/L-PGDS+/+ and CaMKIIαCreERT2/+/L-PGDSflox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIαCreERT2/+/L-PGDS+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIαCreERT2/+/L-PGDSflox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.

Enhancement of angucycline production by combined UV mutagenesis and ribosome engineering and fermentation optimization in Streptomyces dengpaensis XZHG99T.

Strain improvement of Streptomyces dengpaensis XZHG99T was performed by combined UV mutagenesis and ribosome engineering, as well as fermentation optimization for enhanced angucycline production (rabelomycin and saquayamycin B1). First, four streptomycin-resistant mutants were obtained after screening of UV mutagenesis and ribosome engineering. Then a rpsL mutant (HTT7) with higher productivity of rabelomycin and saquayamycin B1 was selected according to genetic screening and HPLC/LC-MS analyses, whose maximum titers of rabelomycin and saquayamycin B1 were 3.6 ± 0.02 mg/L and 7.5 ± 0.04 mg/L, respectively, about fourfold higher than those produced by XZHG99T. Next, fermentation optimization of HTT7 was successively carried out by single-factor experiments in shake flasks. The titers of rabelomycin and saquayamycin B1 were increased to 11.2 ± 0.04 mg/L and 20.5 ± 0.02 mg/L after optimization of shake flask fermentation conditions, respectively, which was increased about sixfold compared with those produced by XZHG99T. Finally, the titers of rabelomycin and saquayamycin B1 reached 15.7 ± 0.05 mg/L and 39.9 ± 0.05 mg/L after the scaled-up fermentation, which was 7.8-fold and 11.4-fold higher than those produced by XZHG99T, respectively. These data demonstrate that the combined empirical strain-breeding approaches are still an effective and convenient pathway to improve strain production ability.

Novel evidence for oncogenic piRNA-823 as a promising prognostic biomarker and a potential therapeutic target in colorectal cancer.

piRNA-823 as a member of the piRNA family is reported to promote tumour cell proliferation in multiple myeloma and hepatocellular cancer. However, few studies on the function of piRNA-823 in colorectal cancer (CRC). Our present study data showed that piRNA-823 plays an oncogene role in CRC cells. Inhibition of piRNA-823 can significantly inhibit the proliferation, invasion and apoptosis resistance of CRC cells. Mechanism studies have shown that piRNA-823 inhibits the ubiquitination of hypoxia-inducible factor-1 alpha (HIF-1α) by up-regulating the expression of Glucose-6-phosphate dehydrogenase (G6PD) and ultimately up-regulates the glucose consumption of carcinoma cells and inhibits the content of intracellular reactive oxygen species (ROS). Therefore, we speculate piRNA-823 promotes the proliferation, invasion and apoptosis resistance of CRC cells by regulating G6PD/HIF-1α pathway. In this study, we set up the cancer-promoting function recovery experiment of piRNA-823 by silencing G6PD gene to confirm the dominance of the above-mentioned pathways. Using clinical samples, we found that overexpression of piRNA-823 correlated with poor overall survival and predicted a poor response to adjuvant chemotherapy of patients with CRC. In a word, our research has further enriched the theory of piRNA-823 promoting the progression of CRC, and laid a solid foundation for the development of piRNA-823-based gene therapy for CRC and its use as a promising prognostic biomarker in CRC patients.

Activation mechanisms and multifaceted effects of mast cells in ischemia reperfusion injury.

Mast cells (MCs) are tissue resident effector cells that form an important part of the immune system's first-line of defence against various pathogenic challenges. They are well known for their roles in anaphylaxis and allergy; however, increasing evidence implicates MCs in a wide range of pathologies. Ischemia/reperfusion (I/R) injury elicits an inflammatory response and triggers the program of tissue damage and restoration, as well as immune regulation. MCs are uniquely distributed around microvasculature and potentially the first responders to early or specific aspects of IR pathogenesis through the release of preformed mediators of MC granule. Versatility and extreme heterogeneity are hallmarks of MCs, resulting from different adaptions acquired during phylogenesis; such plasticity is also highlighted during MC development. Thus, it is necessary to discuss the functions of the MC population that could differ depending on the tissue in which they reside, and various effects of MCs can be induced by stimuli during I/R. In this review, we primarily discuss the contribution of MC activation in I/R injuries of hepatic, pulmonary, myocardial, cerebral, renal, and intestinal organs or systems. A further understanding of the mechanisms underlying the role of MCs in I/R injuries would aid the development of specific MC-targeted therapeutics to protect against some specific injury, such as negating the proinflammatory roles of some specific MC mediators.

Streptomyces tibetensis sp. nov., an actinomycete isolated from the Tibetan Plateau.

A novel actinomycete, designated strain XZ 46T, was isolated from acid sandy soil collected from the Tibetan Plateau, China. Its taxonomic position was determined using a polyphasic approach. Strain XZ 46T shows the typical morphological and chemotaxonomic features of members of the genus Streptomyces: slightly yellow to brown substrate mycelia and grayish white to slightly yellow aerial hyphae forming cylindrical and spiny spores; meso-diaminopimelic acid in the cell wall peptidoglycan; MK-9(H8), MK-9(H4) and MK-9(H2) as predominant menaquinones; diphosphatidylglycerol, phospatidylethanolamine, phosphatidylglycerol and phosphatidylinositol as main polar lipids; and iso-C15:0, iso-C16:0 and anteiso-C15:0 as major cellular fatty acids. The G+C content of the draft genome sequence, consisting of 8,995,813 bp, is 71.23%. The16S rRNA gene sequence analysis indicated that strain XZ 46T shows high sequence similarity to Streptomyces luteogriseus NBRC 13402T as well as forming an independent lineage clade with it in phylogenetic trees. Multilocus sequence analysis (MLSA) of five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) illustrated that Streptomyces hawaiiensis is also a very closely related taxon. However, DNA-DNA hybridization, MLSA evolutionary distance and phenotypic properties demonstrate that strain XZ 46T can be distinguished from these phylogenetically related Streptomyces species. Therefore, it is concluded that strain XZ 46T represents a novel species of the genus Streptomyces, for which the name Streptomyces tibetensis is sp. nov. proposed. The type strain is XZ 46T (= CGMCC 4.7579T = KCTC 49221T).

miR-139-5p reverses stemness maintenance and metastasis of colon cancer stem-like cells by targeting E2-2.

Colon cancer stem cells (CCSCs) stand for a critical subpopulation of colon cancer cells that possess self-renewal and multilineage differentiation potentials and drive tumorigenicity. Due to their impact on treatment tolerance, CCSCs have been a hot research topic in the past few years. We have previously reported that miR-139-5p is a vital tumor repressive noncoding RNA whose level decreases in the clinical colon cancer samples with the increase of tumor malignancy. This research discovered that miR-139-5p targets the Wnt/ß-catenin/TCF7L2 downstream effector E2-2 in CCSCs. E2-2 is a pivot molecule in the negative feedback loop of miR-139-5p/Wnt/ß-catenin/TCF7L2. Its small interfering RNA reverses the stemness maintenance and epithelial-mesenchymal transition of colon cancer CSCs. This study provides a theoretical foundation for the clinical diagnosis and medical treatment of recurrent or metastatic colon cancer with miR-139-5p and its target E2-2.

Key candidate genes of STAT1 and CXCL10 in melanoma identified by integrated bioinformatical analysis.

The underlying mechanisms and gene signatures of melanoma are unknown. In this study, three expression profile data sets (GSE65568, GSE100050, GSE114445) were integrated to identify candidate genes explaining the pathways and functions of melanoma. Expression data sets including 24 melanoma tumours and 13 normal skin samples were merged and analysed in detail. The three GSE profiles shared 431 differentially expressed genes (DEGs), including 227 upregulated genes, 200 downregulated genes and 4 differentially regulated genes. Moreover, the functions and signalling pathways of the shared DEGs with significant p-values were identified. The two most significant modules were filtered from the DEGs protein-protein interaction (PPI) network, which consisted of 284 nodes. We also plotted the prognostic value of hub genes from an online database. In summary, using integrated bioinformatic analysis, we have identified candidate DEGs and pathways in melanoma that could improve our understanding of the causes and underlying molecular events of melanoma, and these candidate genes and pathways could be therapeutic targets for melanoma.