Cardiovascular disease (CVD) is highly prevalent in an ageing society. The increased incidence and mortality rates of CVD are global issues endangering human health. There is an urgent requirement ...for understanding the aetiology and pathogenesis of CVD and developing possible interventions for preventing CVD in ageing hearts. It is necessary to select appropriate models and treatment methods. The D‐galactose‐induced cardiac ageing model possesses the advantages of low mortality, short time and low cost and has been increasingly used in the study of cardiovascular diseases in recent years. Therefore, understanding the latest progress in D‐galactose‐induced cardiac ageing is valuable. This review highlights the recent progress and potential therapeutic interventions used in D‐galactose‐induced cardiac ageing in recent years by providing a comprehensive summary of D‐galactose‐induced cardiac ageing in vivo and in vitro. This review may serve as reference literature for future research on age‐related heart diseases.
A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present ...study a novel metastasis‐related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial‐mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down‐regulation of epithelial markers (E‐cadherin and β‐catenin) and up‐regulation of mesenchymal markers (fibronectin, N‐cadherin, α‐SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. Conclusion: EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. (HEPATOLOGY 2010.)
Exploring new type of synapse–like electronic devices with fusion of computing and memory is a promising strategy to fundamentally approach to intelligent machines. Herein, organic thin film ...memristors (OTFMs) are achieved, functioning as electrically programmable and erasable analog memory with continuous and nonvolatile device states. The memristive characteristics of OTFMs stem from the asymmetric electrode configuration and the cumulative charge trapping/detrapping in a polymer electret layer, which enables the state–dependent current modulation analogous to the synaptic weight change in biological synapses. OTFMs are demonstrated to successfully emulate the essential synaptic functions, including the reversible potentiation and depression, and the short‐term plasticity such as the paired‐pulse facilitation and the long‐term plasticity such as the spike–timing dependent plasticity.
Organic thin film memristors are achieved based on asymmetric electrode configuration and cumulative charge trapping/detrapping in a polymer electret layer, which function as electrically editable and preservable analog memory. Organic thin film memristors are demonstrated to be capable of emulating both short‐term and long‐term synaptic plasticity, such as the paired‐pulse facilitation and spike‐timing‐dependent plasticity.
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with significantly high prevalence in Southern China. Unlike other head and neck cancers, mutations or deletions of tumor suppressor ...genes in NPC are not common. Recently, downregulation of tumor suppressor genes expression by microRNA (miRNA) is increasingly recognized as an important mechanism of nasopharyngeal tumorigenesis. In this study, we reported that microRNA-144 (miR-144) was frequently upregulated in NPC specimens and cell lines. Repression of miR-144 significantly decreased cell proliferation, clonogenicity, migration, invasion and tumor formation in nude mice, while restoring miR-144 in miR-144-attenuated NPC cells exhibited a strong tumorigenic role. Further, we found that miR-144 was inversely correlated with the tumor suppressor gene phosphatase and tensin homolog (PTEN) in NPC specimens and cell lines, and then we identified PTEN as a direct target of miR-144 in NPC cell lines. PTEN downregulation in miR-144-attenuated cells could increase cell growth, migration and invasion. Mechanistic investigations revealed that miR-144 suppressed the expression of PTEN to increase the expression of pAkt and cyclin D1 to promote G(1)-phase transition and decrease E-cadherin to promote migration and invasion. Taken together, we provide compelling evidence that miR-144 functions as an onco-miRNA in NPC, and its oncoeffects are mediated chiefly by repressing PTEN expression to activate the PI3K/Akt pathway.
IL-17A is a pro-inflammatory cytokine that plays important role in inflammatory disease pathology and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the ...progression of hepatocellular carcinoma (HCC).
Expression pattern of IL-17A in clinical HCC samples (n = 43) was determined by immunohistochemistry staining. Transcript levels of MMP2, MMP9 and IL-17A were measured in another 50 pairs (including tumor and related non-tumor tissues) HCC samples. Cell growth, focus formation, cell migration, invasion and western blot assays were used to characterize the functional and signaling mechanisms in IL-17A-treated HCC. Association study was used to identify clinical significance of IL-17A in HCC. Compared with paired non-tumor tissue, higher frequency of IL-17A-positive cells was detected in tumor tissues in HCCs with metastasis, and the frequency of IL-17A-positive cells was also significantly associated with poor prognosis of HCC (P = 0.01). Functional study found that IL-17A could promote HCC cell migration and invasion. Further molecular analysis also showed that IL-17A could upregulate MMP2 and MMP9 expression via NF-κB signaling activation.
IL-17A could promote HCC metastasis by the upregulation of MMP2 and MMP9 expression via activating NF-κB signaling pathway.
Fully integrated ultrathin, transparent and foldable energy storage devices are essential for the development of smart wearable electronics, yet typical supercapacitor electrodes are ...substrate-supported which limits their thickness, transparency and mechanical properties. Employing freestanding transparent electrodes with no substrate support could bring ultrathin, foldable and designable supercapacitors closer to reality. Herein, we report a freestanding, ultrathin (<5 μm), highly conductive (3 × 10 4 S cm −1 ), highly transparent (>84% transmittance) and foldable metallic network electrode, loaded with MnO 2 by electrochemical deposition, as a supercapacitor electrode. The freestanding metallic network electrode is fabricated via a simple and low-cost laser direct-writing micro-patterning technique followed by a selective electrodeposition process, where the metallic network patterns, network periods, metal thickness and also the electrode film patterns can be designed for different applications. The obtained freestanding MnO 2 @Ni network electrode delivers an outstanding areal capacitance of 80.7 mF cm −2 and long-term performance stability (96.3% after 10 000 cycles). Moreover, the symmetric solid-state supercapacitors employing the freestanding MnO 2 @Ni network electrode not only show high areal capacitance as well as high optical transparency (>80% transmittance), but also can be tailored, attached, folded, rolled up, and crumpled into any object or various shapes with only slight performance degradation. The advent of such freestanding transparent metallic network electrodes may open up a new avenue for realizing fully integrated ultrathin, foldable and designable supercapacitors towards self-powered wearable electronics.
With the rapid development of conductive polymers, they have shown great potential in room-temperature chemical gas detection, as their electrical conductivity can be changed upon exposure to ...oxidative or reductive gas molecules at room temperature. However, due to their relatively low conductivity and high affinity toward volatile organic compounds and water molecules, they always exhibit low sensitivity, poor stability, and gas selectivity, which hinder their practical gas sensor applications. In addition, inorganic sensitive materials show totally different advantages in gas sensors, such as high sensitivity, fast response to low concentration analytes, high surface area, and versatile surface chemistry, which could complement the conducting polymers in terms of the sensing characteristics. It seems to be a win-win choice to combine inorganic sensitive materials with polymers for gas detection due to their synergistic effects, which has attracted extensive interests in gas-sensing applications. In this review, we summarize the recent development in polymer-inorganic nanocomposite based gas sensors. The roles of inorganic nanomaterials in improving the gas-sensing performances of conducting polymers are introduced and the progress of conducting polymer-inorganic nanocomposites including metal oxides, metal, carbon (carbon nanotube, graphene), and ternary composites are presented. Finally, a conclusion and a perspective in the field of gas sensors incorporating conducting polymer-inorganic nanocomposite are summarized.
Summary
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, ...profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate‐activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age‐related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti‐aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR‐based anti‐aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.
This paper reports new zircon LA-ICP-MS U–Pb age and Hf-isotope, whole-rock major and trace element, and Sr–Nd isotope data from Cambrian metavolcanic rocks in the central Lhasa subterrane of ...southern Tibet. These rocks form a bimodal volcanic suite consisting mainly of silicic metavolcanic rocks with subordinate metabasalts. Five silicic metavolcanic samples dated at ca. 492Ma and one metabasalt sample yielding a near-concordant 206Pb/238U age of 492±4Ma indicate that mafic and silicic eruptions were contemporaneous. The metabasalts are mostly high-K calc-alkaline, enriched in Th, U, and light rare earth elements (LREEs), and depleted in Nb, Ta, Ti, Zr, and Hf, geochemically resembling the Andean arc basalts. The silicic metavolcanic rocks are high-K calc-alkaline and low in Nb and Zr. The metabasaltic rocks have negative whole-rock εNd(t) values (−4.7 to −3.5) and varying zircon εHf(t) values (−0.7 to +7.5), differing significantly from those of the silicic metavolcanic rocks, which yield negative whole-rock εNd(t) values of −8.4 to −7.2 and varying zircon εHf(t) values (−13.9 to −4.6). The metabasaltic rocks are interpreted as resulting from partial melting of an enriched lithospheric mantle source that was metasomatized by subduction-related components, whereas the silicic metavolcanic rocks were derived from basaltic melt-induced anatexis of the ancient Lhasa basement with inherited mantle melt signatures. The Western Qiangtang–Amdo–Tethyan Himalaya situated in the Indian proto-Tethyan margin and the Lhasa and other possible microcontinents or terranes (e.g., Gongshan, Baoshan, Tengchong, Burma, and Sibumasu) paleographically located in the Australian proto-Tethyan margin represent an early Paleozoic Andean-type magmatic arc facing the proto-Tethyan Ocean. The emplacement of the bimodal volcanic rocks and the development of the Cambro–Ordovician angular unconformity in the central Lhasa subterrane can be attributed to slab break-off of the proto-Tethyan Ocean lithosphere following the collisional accretion of microcontinents or terranes located outboard of the magmatic arc (possibly Eastern Qiangtang and South China).
► Cambrian bimodal volcanic suite in the Lhasa Terrane was emplaced at ca. 492Ma. ► Metabasaltic rocks exhibit geochemical signatures of continent–arc basalts. ► The Lhasa Terrane represents part of an early Paleozoic Andean-type magmatic arc. ► The generation of the bimodal metavolcanic rocks may be a result of slab break-off.
Loss of 16q is one of the most frequent alterations in many malignancies including hepatocellular carcinomas (HCC), suggesting the existence of a tumor suppressor gene (TSG) within the frequently ...deleted region. In this report we describe the identification and characterization of one candidate TSG, tyrosine aminotransferase gene (TAT), at 16q22.1. Loss of one TAT allele was detected in 27/50 (54%) of primary HCCs by quantitative real‐time polymerase chain reaction. In addition, homo‐deletion of TAT alleles was detected in two cases. Down‐regulation of TAT was detected in 28/50 (56%) of HCCs, which was significantly associated with the loss of TAT allele and hypermethylation of TAT 5′ CpG island (CGI) region (P < 0.001). Functional studies found that TAT has a strong tumor suppressive ability. Introduction of the TAT gene into HCC cell lines could effectively inhibit colony formation in soft agar, foci formation, and tumor formation in nude mice. Further study found that the tumor suppressive mechanism of TAT was associated with its proapoptotic role in a mitochondrial‐dependent manner by promoting cytochrome‐c release and activating caspase‐9 and PARP. Conclusion: Taken together, our findings suggest that TAT plays an important suppressive role in the development and progression of HCC. HEPATOLOGY 2010
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