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Background: It is worthwhile to establish a prognostic prediction model based on microenvironment cells (MCs) infiltration and explore new treatment strategies for triple-negative breast cancer (TNBC). Methods: The xCell algorithm was used to quantify the cellular components of the TNBC microenvironment based on bulk RNA sequencing (bulk RNA-seq) data. The MCs index (MCI) was constructed using the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression analysis. Single-cell RNA sequencing (scRNA-seq), spatially resolved transcriptomics (SRT), and multiplex immunofluorescence (mIF) staining analyses verified MCI. The mechanism of action of the MCI was investigated in tumor-bearing mice. Results: MCI consists of the six types of MCs, which can precisely predict the prognosis of the TNBC patients. scRNA-seq, SRT, and mIF analyses verified the existence and proportions of these cells. Furthermore, combined with the spatial distribution characteristics of the six types of MCs, an MCI-enhanced (MCI-e) model was constructed, which could predict the prognosis of the TNBC patients more accurately. More importantly, inhibition of the insulin signaling pathway activated in the cancer cells of the MCIhigh the TNBC patients significantly prolonged the survival time of tumor-bearing mice. Conclusions: Overall, our results demonstrate that MCs infiltration can be exploited as a novel indicator for the prognosis and therapeutic regimen selection of the TNBC patients. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common type of primary malignant bone tumor, which has a high incidence rate in children and adolescents. This research aims to reveal the role of long intergenic non-protein coding RNA 00460 (LINC00460) in OS by the loss-of-function experiment. LINC00460 is involved in the development of multiple types of tumor, but the role of LINC00460 in OS is unclear. To discover more effective molecular targets for the treatment of OS, the association between LINC00460 and OS prognosis was analyzed using the Gene Expression Profiling Interactive Analysis database. Additionally, small interfering RNA was used to knockdown LINC00460 gene expression in vitro to verify its biological effects on the viability, invasive and migratory potential of OS cells. LINC00460 knockdown significantly reduced the viability of OS cells and initiated cell cycle arrest within the G0/G1 phase through the decreased expression of cyclin D1 and CDK4/CDK6. In addition, LINC00460 knockdown promoted apoptosis of OS cells, and inhibited the migratory and invasive abilities of OS cells through the inhibition of the epithelial-mesenchymal transition pathway. In conclusion, the present study reported that LINC00460 may predict OS prognosis, and may serve an important role in mediating the viability, invasive and migratory potential of OS cells. Based on these findings, LINC00460 demonstrated promising potential as a future therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

Background. Type 2 diabetes mellitus (T2DM) has become a chronic disease, serious harm to human health. Complications of the blood pipe are the main cause of disability and death in diabetic patients, including vascular lesions that directly affects the prognosis of patients with diabetes and survival. This study was to determine the influence of high glucose and related mechanism of vascular lesion of type 2 diabetes mellitus pathogenesis. Methods. In vivo aorta abdominalis of GK rats was observed with blood pressure, heart rate, hematoxylin and eosin (H&E), Masson, and Verhoeff staining. In vitro cells were cultured with 30 mM glucose for 24 h. RT-QPCR was used to detect the mRNA expression of endothelial markers PTEN, PI3K, Akt, and VEGF. Immunofluorescence staining was used to detect the expression of PTEN, PI3K, Akt, and VEGF. PI3K and Akt phosphorylation levels were detected by Western blot analysis. Results. Heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure in the GK control group were higher compared with the Wistar control group and no difference compared with the GK experimental model group. Fluorescence intensity of VEGF, Akt, and PI3K in the high-sugar stimulus group was stronger than the control group; PTEN in the high-sugar stimulus group was weakening than the control group. VEGF, Akt, and PI3K mRNA in the high-sugar stimulus group were higher than the control group; protein expressions of VEGF, Akt, and PI3K in the high-sugar stimulus group were higher than the control group. PTEN mRNA in the high-sugar stimulus group was lower than the control group. Protein expression of PTEN in the high-sugar stimulus group was lower than the control group. Conclusions. Angiogenesis is an important pathogenesis of T2DM vascular disease, and PTEN plays a negative regulatory role in the development of new blood vessels and can inhibit the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Nanocatalysts that boost the sluggish kinetics of oxygen reduction reaction with a long-term durability are crucial for widespread use of low-temperature fuel cells. Here we report a nanoporous intermetallic compound typically composed of platinum–cobalt–aluminum intermetallic core with in-situ grown atomic-layer-thick Pt skin as a novel oxygen-reduction-reaction nanocatalyst with remarkably enhanced performance. Both Pt and Co atoms thermodynamically prefer to locate nearby Al element within face-centered cubic Pt 3 Al matrix via the formation of strong Pt Al and Co Al bonds, which not only enable synergistic ligand and compressive strain effects to moderately weaken the oxygen adsorption energy of Pt skin, but alleviate the evolution of surface Pt atoms to protect against the further dissolution of less-noble Co and Al. As a result, the nanoporous platinum–cobalt–aluminum nanocatalyst exhibits specific activity of 3.40 mA cm−2 Pt and mass activity of 2.2 A mg−1 Pt for the oxygen reduction reaction at 0.9 V versus reversible hydrogen electrode (∼13- and ∼20-fold enhancement relative to commercially available platinum nanoparticles supported carbon) with an exceptional durability, showing genuine potential as cathode catalyst in next-generation electrochemical energy conversion devices. Graphical abstract Image 1 Highlights • Scalable preparation of nanoporous Pt Co Al ternary intermetallic compound as ORR catalysts. • Nanoporous Pt Co Al intermetallic compound had a (Pt 1-x Co x) 3 Al/Pt core/shell structure. • Intermetallic compound was employed as matrix to control compressive strain of co incorporation. • Nanoporous Pt Co Al exhibited superior catalytic activity and stability for ORR. [ABSTRACT FROM AUTHOR]

Abstract: Tremendous demands for renewable hydrogen generated from water splitting have stimulated intensive research on developing earth‐abundant, non‐noble, and versatile metal catalysts toward the hydrogen evolution reactions (HER). Here, self‐supported Cu‐Ni‐Al hybrid electrodes that are composed of electroactive Al7Cu4Ni@Cu4Ni core/shell nanocrystals seamlessly integrated in self‐supported 3D bimodal nanoporous Cu skeleton (Bi‐NP Cu/Al7Cu4Ni@Cu4Ni) as robust HER electrocatalysts in alkaline electrolyte are reported. As a result of the proper architecture, in which the Bi‐NP Cu skeleton not only facilitates both electron and electrolyte transports but also provides high specific surface areas to fully use high electrocatalytic activity of Al7Cu4Ni@Cu4Ni core/shell nanocrystals, the Bi‐NP Cu/Al7Cu4Ni@Cu4Ni hybrid catalysts exhibit a low onset overpotential of 60 mV and a small Tafel slope of 110 mV dec−1, enabling the catalytic current density of 10 mA cm−2 at a low overpotential of 139 mV. The highly stable electrochemical performance makes them promising candidates as cathode catalysts in alkaline‐based devices. [ABSTRACT FROM AUTHOR]