Edge computing is proposed to solve the problem of centralized cloud computing caused by a large number of IoT (Internet of Things) devices. The IoT protocols need to be modified according to the ...edge computing paradigm, where the edge computing devices for analyzing IoT data are distributed to the edge networks. The MQTT (Message Queuing Telemetry Transport) protocol, as a data distribution protocol widely adopted in many international IoT standards, is suitable for cloud computing because it uses a centralized broker to effectively collect and transmit data. However, the standard MQTT may suffer from serious traffic congestion problem on the broker, causing long transfer delays if there are massive IoT devices connected to the broker. In addition, the big data exchange between the IoT devices and the broker decreases network capability of the edge networks. The authors in this paper propose a novel MQTT with a multicast mechanism to minimize data transfer delay and network usage for the massive IoT communications. The proposed MQTT reduces data transfer delays by establishing bidirectional SDN (Software Defined Networking) multicast trees between the publishers and the subscribers by means of bypassing the centralized broker. As a result, it can reduce transmission delay by 65% and network usage by 58% compared with the standard MQTT.
Diallyl trisulfide (DATS) is a promising small molecule phytochemical that exhibits in vitro and in vivo activity in multiple preclinical solid tumor models including breast cancer, but the ...underlying mechanism is not fully understood. We have shown previously that forkhead box Q1 (FoxQ1) transcription factor is a novel target for breast cancer stem‐like cells (bCSC) inhibition by DATS. Analysis of the breast TCGA (The Cancer Genome Atlas) data revealed that FoxQ1 expression was positively associated with that of SLC16A1/monocarboxylate transporter 1 (MCT1). Western blot analysis confirmed increased expression of MCT1 protein in SUM159 (basal‐like) and MCF‐7 cells (luminal‐type) stably transfected to overexpress FoxQ1. Furthermore, FoxQ1 was recruited to the promoter of SLC16A1/MCT1. Treatment of SUM159 and MCF‐7 cell lines with DATS resulted in suppression of MCT1 protein level that was accompanied by a decrease in intracellular and secreted levels of lactate. Overexpression or knockdown of MCT1 protein failed to alter DATS‐mediated inhibition of colony formation or cell migration when compared to corresponding control cells. On the other hand, overexpression of MCT1 protein conferred partial but statistically significant protection against DATS‐mediated inhibition of bCSC fraction (CD49fhigh/CD44high and aldehyde dehydrogenase 1 activity). The size of the mammospheres was relatively smaller in the DATS‐treated group compared to control group. Inhibition of bCSC upon DATS treatment was augmented by knockdown of the MCT1 protein. In conclusion, the present study reveals that MCT1 is a novel target for bCSC inhibition by DATS treatment.
The FoxQ1 is an oncogenic transcription factor that is overexpressed in basal‐like and luminal‐type human breast cancers when compared to the normal mammary tissue. The FoxQ1 is implicated in mammary ...tumor progression. However, the mechanism by which FoxQ1 promotes mammary tumorigenesis is not fully understood. In this study, we present experimental evidence for a novel function of FoxQ1 in the regulation of complex I activity of the electron transport chain. The RNA‐seq data from FoxQ1 overexpressing basal‐like SUM159 cells revealed a statistically significant increase in the expression of complex I subunits NDUFS1 and NDUFS2 when compared to the empty vector (EV) transfected control cells. Consistent with these results, the basal and ATP‐linked oxygen consumption rates were significantly increased by FoxQ1 overexpression in SUM159 and luminal‐type MCF‐7 cells. The FoxQ1 overexpression in both cell lines resulted in increased intracellular levels of pyruvate, lactate, and ATP that was associated with overexpression of pyruvate dehydrogenase and pyruvate carboxylase proteins. Activity and assembly of complex I were significantly enhanced by FoxQ1 overexpression in SUM159 and MCF‐7 cells that correlated with increased mRNA and/or protein levels of complex I subunits NDUFS1, NDUFS2, NDUFV1, and NDUFV2. The chromatin immunoprecipitation assay revealed the recruitment of FoxQ1 at the promoters of both NDUFS1 and NDUFV1. The cell proliferation of SUM159 and MCF‐7 cells was increased significantly by overexpression of NDUFS1 as well as NDUFV1 proteins. In conclusion, we propose that increased complex I‐linked oxidative phosphorylation is partly responsible for oncogenic role of FoxQ1 at least in human breast cancer cells.
Bone is the most prone to metastatic spread of breast cancer cells for each subtype of the disease. Bone metastasis‐related complications including severe pain and pathological fractures affect ...patients' quality of life. Current treatment options including surgery, radiation, and bone‐targeted therapies (e.g., bisphosphonates) are costly or have serious adverse effects such as renal toxicity and osteonecrosis of the jaws. Therefore, a safe, inexpensive, and efficacious agent for prevention of breast cancer bone metastasis is urgently needed. Our previously published RNA sequencing analysis revealed that many genes implicated in bone remodeling and breast cancer bone metastasis were significantly downregulated by treatment with withaferin A (WA), which is a promising cancer chemopreventive agent derived from a medicinal plant (Withania somnifera). The present study investigated whether WA inhibits breast cancer induction of osteoclast differentiation. At plasma achievable doses, WA treatment inhibited osteoclast differentiation (osteoclastogenesis) induced by three different subtypes of breast cancer cells (MCF‐7, SK‐BR‐3, and MDA‐MB‐231). WA and the root extract of W. somnifera were equally effective for inhibition of breast cancer induction of osteoclast differentiation. This inhibition was accompanied by suppression of interleukin (IL)‐6, IL‐8, and receptor activator of nuclear factor‐κB ligand, which are pivotal osteoclastogenic cytokines. The expression of runt‐related transcription factor 2, nuclear factor‐κB, and SOX9 transcription factors, which positively regulate osteoclastogenesis, was decreased in WA‐treated breast cancer cells as revealed by confocal microscopy and/or immunoblotting. Taken together, these data suggest that WA could be a promising agent for prevention of breast cancer‐induced bone metastasis.
Polyacrylonitrile (PAN) based carbon nanofibers (CNFs) show enormous potential as a high performance and cost-effective supercapacitor electrode material. However, there are two intrinsic limitations ...that prevent their deployment in this field, namely their low surface area and limited transporting channels for ion diffusion. Here, we design an approach that concurrently addresses both problems. We employ electrospinning of PAN and zeolitic imidazolate framework (ZIF-8) nanoparticles to fabricate highly porous CNFs, followed by a sodium borohydride treatment and freeze-drying to maintain the three-dimensionalities of carbon nanofibers networks. Nitrogen and boron co-doping could be achieved together by controlling the conditions for stabilization and carbonization after the ammonium borate tri-hydrate treatment. The novel ZIF-8 incorporated 3D nitrogen and boron co-doped carbon nanofiber electrode was tested as a binder-free supercapacitor electrode and delivered a high specific capacitance of 295 F g−1 at a 0.5 A g−1 current density, exceeding that of PAN-based carbon nanofiber supercapacitor electrodes. Indeed, the novel electrode also maintained a high rate capability and remarkable cyclic stability of 94.5% capacitance retention even after 10 000 charge-discharge cycles. This superior electrochemical performance is attributed to the large surface area, mesoporous nature and high wettability of the B and N doped carbon nanofiber electrode. This study will inspire the development of new 3D PAN and metal organic framework based porous electrode materials for high performance energy storage devices.
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Forkhead Box Q1 (FoxQ1) transcription factor is overexpressed in luminal-type and basal-type human breast cancers when compared to normal mammary tissue. This transcription factor is best known for ...its role in promotion of breast cancer stem-like cells and epithelial to mesenchymal transition. The present study documents a novel function of FoxQ1 in breast cancer cells. Overexpression of FoxQ1 in basal-like SUM159 cells and luminal-type MCF-7 cells resulted in increased conversion of microtubule-associated protein light chain 3 beta-I (LC3B-I) to LC3B-II, which is a hallmark of autophagy. Autophagy induction by FoxQ1 overexpression was confirmed by visualization of LC3B puncta as well as by transmission electron microscopy. Expression profiling for genes implicated in autophagy regulation revealed upregulation of many genes, including ATG4B, ATG16L1, CTSS, CXCR4 and so forth but downregulation of BCL2L1, DRAM1, TNF, ULK2 and so forth by FoxQ1 overexpression in SUM159 cells. Western blot analysis confirmed upregulation of ATG4B and CXCR4 proteins by FoxQ1 overexpression in both SUM159 and MCF-7 cells. Chromatin immunoprecipitation assay revealed recruitment of FoxQ1 at the promoter of ATG4B. Pharmacological inhibition of ATG4B using S130 significantly increased apoptosis induction by DOX in empty vector transfected as well as FoxQ1 overexpressing SUM159 and MCF-7 cells but this effect was statistically significantly lowered by FoxQ1 overexpression indicating the protective role of FoxQ1 on apoptosis. Treatment of SUM159 cells with S130 and DOX enhanced LC3B-II level in both empty vector transfected cells and FoxQ1 overexpressing SUM159 cells but not in FoxQ1 overexpressing MCF-7 cells. In conclusion, FoxQ1 is a novel regulator of autophagy.
Withaferin A (WA) exhibits cancer chemopreventive efficacy in preclinical models representative of two different subtypes of breast cancer. However, the mechanism(s) underlying breast cancer ...chemoprevention by WA is not fully elucidated. We performed RNA‐seq analyses using a non‐tumorigenic mammary epithelial cell line (MCF‐10A) and human breast cancer cells (BCC) belonging to the luminal‐type (MCF‐7), HER2‐enriched (SK‐BR‐3), and basal‐like subtype (MDA‐MB‐231) to identify novel cancer‐selective mechanistic targets of WA. The WA‐regulated transcriptome was strikingly different between MCF‐10A versus BCC. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed downregulation of genes associated with cellular senescence in WA‐treated BCC. Consequently, the number of senescence‐associated β‐galactosidase positive cells was decreased significantly in WA‐treated BCC but not in the MCF‐10A cells. WA treatment caused upregulation of senescence marker p21 more robustly in BCC than in MCF‐10A. Breast cancer prevention by WA in rats was also associated with upregulation of p21 protein expression. The Reactome pathway analyses indicated upregulation of genes associated with cellular response to stress/external stimuli in WA‐treated BCC but not in MCF‐10A. Two proteins represented in these pathways (HSPA6 and NRF2) were further investigated. While HSPA6 was dispensable for WA‐mediated apoptosis and autophagy or inhibition of cell migration, the NRF2 knockout cells were more resistant to apoptosis resulting from WA treatment than control cells. Finally, expression of some glycolysis‐related proteins was decreased by WA treatment both in vitro and in vivo. In summary, this study provides novel insights into cancer‐selective pathways affected by WA that may contribute to its chemopreventive efficacy in breast cancer.
Zeolitic imidazolate framework-8 (ZIF-8)-derived nanoporous carbons (NPCs) have become more attractive in the energy storage sector due to their excellent characteristics, such as their porosity, ...available specific surface area, and charge storing ability. In this work, we further modify ZIF-8NPC by using Co3O4 nanoflakes together with polyaniline (PANI) in a controlled in situ polymerization on the surface of ZIF-8NPC to form a Co3O4-PANI@ZIF-8NPC nanocomposite. The as-prepared nanocomposite shows a high specific capacitance of 1407 F g−1 at 1 A g−1 with remarkable rate capability and cyclic stability. An asymmetric supercapacitor (ASC) with Co3O4-PANI@ZIF-8NPC as a positive electrode and ZIF-8NPC as a negative electrode shows a high energy densities of 52.81 W h kg−1 (at a power density of 751.51 W kg−1) and 18.75 W h kg−1 (at a power density of 7500 W kg−1), along with a high cyclic stability as evidenced by retaining 88.43% of the initial capacitance after 10,000 cycles at 10 A g−1. The remarkable electrochemical performance mentioned above is attributed to a synergistic effect between the high conductivity provided by PANI, the increased number of pseudocapacitive active sites provided by CO3O4, and the high surface area with a suitable pore size distribution provided by ZIF-8NPC. The results demonstrate that the as-prepared electrode materials can be a good alternative for applications in supercapacitors and other energy storage devices.
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•A unique Co3O4-PANI@ZIF-8NPC nanocomposite is designed for supercapacitor applications.•An asymmetric supercapacitor, Co3O4-PANI@ZIF-8NPC//ZIF-8NPC, was assembled and tested.•The synergetic effect between the Co3O4 and PANI-enhanced ZIF-8NPC delivered excellent electrochemical performance.•The ASC showed a high energy density of 52.81 W h kg−1 at a power density of 751.51 W kg−1.
The hurdle of fabricating asymmetric supercapacitor (ASC) devices using a faradic cathode and a double layer anode is challenging due to the required large amount of active mass of anodic material ...compared to that of the cathodic material during mass balancing due to the large difference in capacitance values of the two electrodes. Here, the problem is addressed by engineering a negative electrode that furnishes an ultrahigh capacitance. An in situ developed metal–organic framework (MOF)‐based thermal treatment is adopted to grow highly porous N‐doped carbon nanotubes (CNTs) containing submerged Co nanoparticles over nano‐fibrillated electrospun hollow carbon nanofibers (HCNFs). The optimized CNT@HCNF‐1.5 furnishes an ultrahigh capacitance approaching 712 F g–1 with excellent rate capability. The capacitance reported from this work is the highest for any carbonaceous material reported to date. The CNT@HCNF‐1.5 is further used to fabricate symmetric supercapacitors (SSCs), as well as ASC devices. Remarkably, both the SSC and ASC devices furnish incredible performances in all aspects of SCs, such as a high energy density, long cycle life, and high rate capability, displaying decent practical applicability. The energy density of the SSC device reaches as high as 20.13 W h kg–1, whereas that of ASC approaches 87.5 W h kg–1.
An in situ developed metal–organic framework‐based thermal treatment technique is adopted to prepare porous N‐doped carbon nanotubes containing firmly submerged Co‐nanoparticles over nano‐fibrillated electrospun hollow carbon nanofibers. When the optimized CNT@HCNF‐1.5 is applied as a negative electrode, the problem related to mass balancing during fabrication of asymmetric supercapacitor can be addressed satisfactorily that will open new possibilities for the future works.
A subset of human prostate cancer exhibits increased de novo synthesis of fatty acids, but the molecular driver(s) of this metabolic abnormality remains obscure. This study demonstrates a novel ...metabolic function of c-Myc (Myc) in regulation of fatty acid synthesis. The role of Myc in regulation of fatty acid synthesis was investigated by: (a) interrogation of the prostate cancer The Cancer Genome Atlas (TCGA) dataset, (b) chromatin immunoprecipitation, and (c) determination of the expression of fatty acid synthesis enzymes and targeted metabolomics using a mouse model and human specimens. The expression of MYC was positively associated with that of key fatty acid synthesis genes including ACLY, ACC1, and FASN in prostate cancer TCGA dataset. Chromatin immunoprecipitation revealed Myc occupancy at the promoters of ACLY, ACC1, and FASN. Prostate-specific overexpression of Myc in Hi-Myc transgenic mice resulted in overexpression of ACLY, ACC1, and FASN proteins in neoplastic lesions and increased circulating levels of total free fatty acids. Targeted metabolomics confirmed increased circulating levels of individual fatty acids in the plasma of Hi-Myc mice and human subjects when compared to corresponding controls. Immunohistochemistry also revealed a positive and statistically significant association in expression of Myc with that of ACC1 in human prostate adenocarcinoma specimens. We propose that Myc-regulated fatty acid synthesis is a valid target for therapy and/or prevention of prostate cancer.
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