Abstract Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ ...on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro . The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We focus on the lot-sizing and scheduling problem with the additional considerations of machine eligibility, sequence-dependent setups, and uncertain demands. Multi-stage stochastic programming is ...proposed. We analyze the problem structure and suggest ways for modeling and solving large-scale stochastic integer programs. The analysis compares deterministic and stochastic model solutions to assess demand variance effects under the circumstances of increasing, fluctuating, and decreasing demands. The result shows that the expected cost performance of the stochastic programming model outperforms that of the deterministic model, in particular, when the demand is highly uncertain in the circumstance of an upward market trend. Our study can apply to the wafer fab manufacturing and other industries that heavily restricted by machine eligibility and demand uncertainties.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A unique “clean‐lifting transfer” (CLT) technique that applies a controllable electrostatic force to transfer large‐area and high‐quality CVD‐grown graphene onto various rigid or flexible substrates ...is reported. The CLT technique without using any organic support or adhesives can produce residual‐free graphene films with large‐area processability, and has great potential for future industrial production of graphene‐based electronics or optoelectronics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Energy scavenging has become a fundamental part of ubiquitous sensor networks. Of all the scavenging technologies, solar has the highest power density available. However, the energy source is ...erratic. Integrating energy conversion and storage devices is a viable route to obtain self‐powered electronic systems which have long‐term maintenance‐free operation. In this work, we demonstrate an integrated‐power‐sheet, consisting of a string of series connected organic photovoltaic cells (OPCs) and graphene supercapacitors on a single substrate, using graphene as a common platform. This results in lighter and more flexible power packs. Graphene is used in different forms and qualities for different functions. Chemical vapor deposition grown high quality graphene is used as a transparent conductor, while solution exfoliated graphene pastes are used as supercapacitor electrodes. Solution‐based coating techniques are used to deposit the separate components onto a single substrate, making the process compatible with roll‐to‐roll manufacture. Eight series connected OPCs based on poly(3‐hexylthiophene)(P3HT):phenyl‐C61‐butyric acid methyl ester (PC60BM) bulk‐heterojunction cells with aluminum electrodes, resulting in a ≈5 V open‐circuit voltage, provide the energy harvesting capability. Supercapacitors based on graphene ink with ≈2.5 mF cm−2 capacitance provide the energy storage capability. The integrated‐power‐sheet with photovoltaic (PV) energy harvesting and storage functions had a mass of 0.35 g plus the substrate.
Simultaneous energy harvesting (organic photovoltaic cell) and energy storing (supercapacitor) functionalities are integrated onto a single substrate by using graphene in different forms and qualities. Organic photovoltaic cells provide ≈5 V open‐circuit output to charge the supercapacitor (≈2.5 mF cm−2 capacitance), results in a self‐powered system used to drive RGB light emitting diode.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Blue photoluminescene (PL) from chemically derived graphene oxide has been observed. The PL is attributed to radiative recombination of electron–hole pairs in isolated “molecular” sp2 domains, which ...are present within the carbon–oxygen sp3 matrix in chemically derived graphene oxide. The PL intensity is correlated to the evolution of sp2 domains during reduction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recurrent influenza outbreak has been a concern for government health institutions in Taiwan. Over 10% of the population is infected by influenza viruses every year, and the infection has caused ...losses to both health and the economy. Approximately three million free vaccine doses are ordered and administered to high-risk populations at the beginning of flu season to control the disease. The government recommends sharing and redistributing vaccine inventories when shortages occur. While this policy intends to increase inventory flexibility, and has been proven as widely valuable, its impact on vaccine availability has not been previously reported.
This study developed an inventory model adapted to vaccination protocols to evaluate government recommended polices under different levels of vaccine production. Demands were uncertain and stratified by ages and locations according to the demographic data in Taiwan.
When vaccine supply is sufficient, sharing pediatric vaccine reduced vaccine unavailability by 43% and overstock by 54%, and sharing adult vaccine reduced vaccine unavailability by 9% and overstock by 15%. Redistributing vaccines obtained greater gains for both pediatrics and adults (by 75%). When the vaccine supply is in short, only sharing pediatric vaccine yielded a 48% reduction of unused inventory, while other polices do not improve performances.
When implementing vaccination activities for seasonal influenza intervention, it is important to consider mismatches of demand and vaccine inventory. Our model confirmed that sharing and redistributing vaccines can substantially increase availability and reduce unused vaccines.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A high basal level of autophagic flux in bladder cancer (BC) cells prevents cell death and weakens chemotherapy efficacy. However, how autophagy influences cancer‐associated immunosuppression in BC ...remains undetermined. In this study, we observed a negative correlation between the autophagy‐related markers LC3‐II and programmed death ligand‐1 (PD‐L1) in BC cells. The autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (Baf‐A1) increased PD‐L1 expression in BC cells through the ERK–JNK–c‐Jun signal‐transduction pathway. Moreover, the treatment of BC cells with CQ and Baf‐A1 inhibited hsa‐microRNA‐34a (miR‐34a) expression and miR‐34a overexpression in BC cells prevented the autophagy blockade–induced PD‐L1 expression; a negative correlation between miR‐34a and PD‐L1 expression was observed during treatment with autophagy inhibitors. Furthermore, miR‐34a overexpression induced the cytotoxic activity of natural killer cells against BC cells. Our results provide evidence that autophagy blockade and its regulatory pathway affect cancer‐associated immunosuppression through PD‐L1 elevation. Thus, the coadministration of autophagy inhibitors and a PD‐L1 immune checkpoint blockade provides a potential therapeutic approach for treating BC.
Graphical
Our model illustrates the pharmacological inhibition of autophagy could induce PD‐L1 expression in BC cells through the ERK–JNK–c‐Jun signaling transduction pathway and miR‐34a downregulation, revealing the effect of genetic and epigenetic regulation of autophagy on PD‐L1. In consequence, BC cells expressing PD‐L1 suppress NK cell cytotoxic activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Two types of lap-spliced intermediate hoops were proposed to address the construction difficulty encountered for conventional intermediate hoops or stirrups used in the plastic hinge regions of beams ...of special moment-resisting frames. In the proposed type one hoops, a set of U-bars was lap-spliced to the other set of U-bars. The U-bar set was formed by multiple U-bars welded together by the longitudinal holding wires. Weldable steel wire reinforcement was used. In the proposed type two hoops, two three-dimensional stirrups were lap-spliced to form two intermediate hoops. The lap-splice length was based on the Class B tension lap splice of ACI 318. Three full-scale beam specimens, including two specimens with the proposed lap-spliced intermediate hoops and one control specimen with conventional intermediate stirrups, were tested using lateral cyclic loading. Test results showed that the specimens with the proposed lap-spliced intermediate hoops exhibited better drift capacities, energy dissipation ability, and moment strength than the control specimen. The proposed lap-spliced intermediate hoops were more effective in restraining the buckling of longitudinal bars than the conventional closed stirrups.
Summary
Epidemiological studies have shown that soy consumption is associated with lower incidence of various diseases, such as cancer. Over the past decades, soy proteins and derived peptides have ...been considered as potential preventive agents against the initiation, promotion and progression of cancer. Additionally, soybeans provide essential nutrients and abundant peptides and proteins with multiple bioactivities. Here, we specifically emphasise the chemoprevention property of several soy proteins/peptides, such as lectins, lunasin and protease inhibitors. Moreover, their anti‐inflammatory and antioxidant properties, which have been demonstrated to be associated with chemopreventive properties, are addressed here. Furthermore, computational methods applied in this field are reviewed. Researchers navigate a large volume of data to understand the interactions among the genome, cellular molecules, dietary interventions, medical treatments and diseases. Numerous powerful tools have been recommended for designing an optimal strategy for future anti‐cancer treatments with precise diagnosis and individualised approaches.
Many bioactive compounds are found in soy. Soy proteins and peptides exert anti‐inflammatory and antioxidant properties contributed to chemopreventive properties. Multidisciplinary studies integrate to provide precision medicine for chemoprevention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Autophagy plays a dual function in cancer progression; autophagy activation can support cancer cell survival or contribute to cell death. Miconazole, a Food and Drug Administration‐approved ...antifungal drug, has been implicated in oncology research recently. Miconazole was found to exert antitumor effects in various tumors, including bladder cancer (BC). However, whether it provokes protective autophagy has been never discussed. We provide evidence that miconazole induces protective autophagy in BC for the first time. The results indicated that 1A/1B‐light chain 3 (LC3)‐II processing and p62 expression were elevated after miconazole exposure. Also, adenosine monophosphate‐activated protein kinase phosphorylation was increased after miconazole treatment. We also confirmed the autophagy‐promoting effect of miconazole in the presence of bafilomycin A1 (Baf A1). The result indicates that a combination treatment of miconazole and Baf A1 improved LC3‐II processing, confirming that miconazole promoted autophagic flux. The acridine orange, Lysotracker, and cathepsin D staining results indicate that miconazole increased lysosome formation, revealing its autophagy‐promoting function. Finally, miconazole and autophagy inhibitor 3‐methyladenine cotreatment further reduced the cell viability and induced apoptosis in BC cells, proving that miconazole provokes protective autophagy in BC cells. Our findings approve that miconazole has an antitumor effect in promoting cell apoptosis; however, its function of protective autophagy is needed to be concerned in cancer treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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