Upregulation of Pin1 was shown to advance the functioning of several oncogenic pathways. It was recently shown that Pin1 is potentially an excellent prognostic marker and can also serve as a novel ...therapeutic target for prostate cancer. However, the molecular mechanism of Pin1 overexpression in prostate cancer is still unclear. In the present study, we showed that the mRNA expression levels of Pin1 were not correlated with Pin1 protein levels in prostate cell lines which indicated that Pin1 may be regulated at the post-transcriptional level. A key player in post-transcriptional regulation is represented by microRNAs (miRNAs) that negatively regulate expressions of protein-coding genes at the post-transcriptional level. A bioinformatics analysis revealed that miR-296-5p has a conserved binding site in the Pin1 3′-untranslated region (UTR). A luciferase reporter assay demonstrated that the seed region of miR-296-5p directly interacts with the 3′-UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be inversely correlated with Pin1 expression in prostate cancer cell lines and prostate cancer tissues. Furthermore, restoration of miR-296-5p or the knockdown of Pin1 had the same effect on the inhibition of the ability of cell proliferation and anchorage-independent growth of prostate cancer cell lines. Our results support miR-296-5p playing a tumor-suppressive role by targeting Pin1 and implicate potential effects of miR-296-5p on the prognosis and clinical application to prostate cancer therapy.
•We identified that miR-296-5p is a Pin1 regulatory miRNA in prostate cancer.•Specific 3′-untranslated region of Pin1 mRNA is the direct target of miR-296-5p.•Expression of miR-296-5p and Pin1 was inversely correlated in prostate cancer.•MiR-296-5p playing a tumor-suppressive role by targeting Pin1•Targeting miR-296-5p/Pin1 interaction is new avenue for prostate cancer treatment.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the ...malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
Metal nanowires are promising for their applications including electrical connectors, transparent conductive electrodes and conductive additives, but the use of metal nanowires as photothermal agents ...to convert light to heat has yet to be reported. Here we synthesized dispersible polyethylene glycol-coated (PEGylated) copper nanowires (CuNWs) and showed for the first time that PEGylated CuNWs were able to convert near-infrared (NIR, 808 nm) light into heat at a photothermal efficiency of 12.5%. The PEGylated CuNWs exhibited good reusability and enabled rapid temperature rise to >50 °C in 6 min by NIR irradiation. The PEGylated CuNWs were flexible and intertwined around the cancer cells, which, upon NIR irradiation, allowed for direct heat transmission to cells and effectively triggered cancer cell ablation in vitro. Intratumoral injection of PEGylated CuNWs into colon tumor-bearing mice and ensuing NIR irradiation for 6 min significantly raised the local temperature to >50 °C, induced necrosis, and suppressed tumor growth. Compared with other NIR light absorbing noble metal-based nanomaterials, PEGylated CuNWs are relatively easy to synthesize in both laboratory and large scales using the low cost copper. This study demonstrated the potential of PEGylated CuNWs as a new cost-effective photothermal agent, and paved a new avenue to using CuNWs for cancer therapy.
This article presents a novel static random access memory computing-in-memory (SRAM-CIM) structure designed for high-precision multiply-and-accumulate (MAC) operations with high energy efficiency ...(EF), high readout accuracy, and short compute latency. The proposed device employs 1) a time-domain incremental-accumulation (TDIA) scheme to enable high-accumulation MAC operations while maintaining a large signal margin across MAC values (MACVs), 2) a dynamic differential-reference (D2REF) scheme based on software-hardware co-design to reduce read energy consumption, and 3) a low-dMACV-aware recursive time-to-digital converter (LMAR-TDC) for implementation with the D2REF scheme to further suppress readout energy consumption. A 28 nm 1 Mb SRAM-CIM macro fabricated using foundry-provided compact 6T-SRAM cells achieved EF of 39.31 TOPS/W and compute latency of 6.6 ns for 8b-MAC operations with 64 accumulations per cycle and near-full output precision (22b).
The microalga incorporated photobioreactor is a highly efficient biological system for converting CO₂ into biomass. Using microalgal photobioreactor as CO₂ mitigation system is a practical approach ...for elimination of waste gas from the CO₂ emission. In this study, the marine microalga Chlorella sp. was cultured in a photobioreactor to assess biomass, lipid productivity and CO₂ reduction. We also determined the effects of cell density and CO₂ concentration on the growth of Chlorella sp. During an 8-day interval cultures in the semicontinuous cultivation, the specific growth rate and biomass of Chlorella sp. cultures in the conditions aerated 2-15% CO₂ were 0.58-0.66d⁻¹ and 0.76-0.87gL⁻¹, respectively. At CO₂ concentrations of 2%, 5%, 10% and 15%, the rate of CO₂ reduction was 0.261, 0.316, 0.466 and 0.573gh⁻¹, and efficiency of CO₂ removal was 58%, 27%, 20% and 16%, respectively. The efficiency of CO₂ removal was similar in the single photobioreactor and in the six-parallel photobioreactor. However, CO₂ reduction, production of biomass, and production of lipid were six times greater in the six-parallel photobioreactor than those in the single photobioreactor. In conclusion, inhibition of microalgal growth cultured in the system with high CO₂ (10-15%) aeration could be overcome via a high-density culture of microalgal inoculum that was adapted to 2% CO₂. Moreover, biological reduction of CO₂ in the established system could be parallely increased using the photobioreactor consisting of multiple units.
Large-area conducting transparent conducting electrodes (TCEs) were prepared by a fast, scalable, and low-cost spray deposition of copper nanowire (CuNW) dispersions. Thin, long, and pure copper ...nanowires were obtained via the seed-mediated growth in an organic solvent-based synthesis. The mean length and diameter of nanowires are, respectively, 37.7 μm and 46 nm, corresponding to a high-mean-aspect ratio of 790. These wires were spray-deposited onto a glass substrate to form a nanowire conducting network which function as a TCE. CuNW TCEs exhibit high-transparency and high-conductivity since their relatively long lengths are advantageous in lowering in the sheet resistance. For example, a 2 × 2 cm2 transparent nanowire electrode exhibits transmittance of T = 90% with a sheet resistance as low as 52.7 Ω sq–1. Large-area sizes (>50 cm2) of CuNW TCEs were also prepared by the spray coating method and assembled as resistive touch screens that can be integrated with a variety of devices, including LED lighting array, a computer, electric motors, and audio electronic devices, showing the capability to make diverse sizes and functionalities of CuNW TCEs by the reported method.
Cisplatin-based chemotherapy is the standard treatment for bladder urothelial carcinoma (UC). Most patients experience chemoresistance, the primary cause of treatment failure, which leads to disease ...relapse. The underlying mechanism of chemoresistance involves reduced apoptosis. In this study, we investigated the antitumor effect of the deubiquitylating enzyme inhibitor PR-619 in cisplatin-resistant bladder UC. Deubiquitinase (ubiquitin-specific protease 14 (USP14) and USP21) immunohistochemical staining demonstrated that deubiquitination is related to chemoresistance in patients with metastatic UC and may be a target for overcoming chemoresistance. Cytotoxicity and apoptosis were assessed using fluorescence-activated flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay, and PR-619 was found to enhance the cytotoxic and apoptotic effects of cisplatin in cisplatin-resistant T24/R cells. Mitigated cisplatin chemoresistance was associated with the concurrent suppression of c-Myc expression in T24/R cells. Moreover, the expression of c-Myc was upregulated in human bladder UC specimens from patients with chemoresistance. Experiments in a xenograft nude mouse model confirmed that PR-619 enhanced the antitumor effects of cisplatin. These results are promising for the development of therapeutic strategies to prevent UC chemoresistance through the combined use of chemotherapeutic agents/deubiquitination inhibitors (PR-619) by targeting the c-Myc pathway.
•Protective film was fabricated by integration processes.•Al oxide/Al bi-layer coating is significantly improved the corrosion resistance.•The optimal parameter for anodic aluminum oxidation process ...is 15 min.
Anodic aluminum oxidation (AAO) process on sputtered-Al film to form an oxide coating as an anticorrosion layer on AZ91D magnesium alloy was performed. The cross-sectional scanning electron microscope images showed an increase on the thickness of anodized oxide layer with increasing oxidation duration. By X-ray photoelectron spectroscopy and X-ray diffraction analyses, the anodized alumina layer had an amorphous structure, where the chemical composition is mainly composed of aluminum oxide. From the results of anticorrosion test, the higher charge transfer resistance of oxide layer was obtained for all AAO specimens by electrochemical impedance spectroscopy, as compared to the raw AZ91D substrate. In addition, the potentiodynamic polarization measurement showed that the specimen with 15 min anodizing treatment had the lower corrosion current density (0.29 μA/cm2), and the higher protection efficiency (99.64 %). These results proved that Al oxide/Al bi-layer composite passive film on AZ91D alloys is significantly improved the corrosion resistance behaviors and the optimal parameter for AAO process is 15 min.
: Cancer cells reprogram cellular metabolism to fulfill their needs for rapid growth and metastasis. However, the mechanism controlling this reprogramming is poorly understood. We searched for ...upregulated signaling in metastatic colorectal cancer and investigated the mechanism by which Glut3 promotes tumor metastasis.
: We compared RNA levels and glycolytic capacity in primary and metastatic colon cancer. The expression and association of Glut3 with clinical prognosis in colon cancer tissues was determined by immunohistochemistry. Glut3 gain-of-function and loss-of-function were established using colon cancer HCT116, HT29, and metastatic 116-LM cells, and tumor invasiveness and stemness properties were evaluated. Metabolomic profiles were analyzed by GC/MS and CE-TOF/MS. The metastatic burden in mice fed a high-fat sucrose diet was assessed by intravenous inoculation with Glut3 knockdown 116-LM cells.
: Upregulation of glycolytic genes and glycolytic capacity was detected in metastatic colorectal cancer cells. Specifically, Glut3 overexpression was associated with metastasis and poor survival in colorectal cancer patients. Mechanistically, Glut3 promoted invasiveness and stemness in a Yes-associated protein (YAP)-dependent manner. Activation of YAP in turn transactivated Glut3 and regulated a group of glycolytic genes. Interestingly, the expression and phosphorylation of PKM2 were concomitantly upregulated in metastatic colorectal cancer, and it was found to interact with YAP and enhance the expression of Glut3. Importantly, a high-fat high-sucrose diet promoted tumor metastasis, whereas the inhibition of either Glut3 or YAP effectively reduced the metastatic burden.
: Activation of the Glut3-YAP signaling pathway acts as a master activator to reprogram cancer metabolism and thereby promotes metastasis. Our findings reveal the importance of metabolic reprogramming in supporting cancer metastasis as well as possible therapeutic targets.
Silicone printing can enable a lot more accessibility and customizability towards utilizing silicone in different applications, including medicine for its biocompatibility. However, challenges ...existed for printing in specific geometries due to the lack of guidelines and studies on the mechanical properties. To support the understanding of printing three-dimensional silicone structure having different infill patterns and gel-like material, this paper conducted a parametric study for the specimens printed using a Bowden-type silicone printer and measurements of the tensile properties. Four printing parameters of print speed, infill density, flow rate, and infill pattern, are categorized following the Taguchi L9 method, and arranged into the four-parameter-three-level orthogonal array. The signal-to-noise (S/N) ratio was calculated based on the principle of the-larger-the-better, and analysis of variance (ANOVA) was also obtained. Tensile performance was further discussed with the characterization of internal structure, using the cross-sections of the printed specimens. It was found that the change of flow rate is the most significant to the tensile stress; and for the tensile strain, infill pattern was found to be the most significant parameter. The Line infill pattern consistently presented the highest tensile stress. Agglomeration can be seen inside the printed structure, hence optimal printing parameters play an important role for complicated geometry, while ensuring the flow rate and infill density do not exceed a reasonable value. This study would serve as the guideline for printing three-dimensional silicone structures.
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