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In many human cancers, including hepatocellular carcinoma (HCC), high density of infiltrating tumor-associated macrophages (TAM) is associated with poor prognosis. Most TAMs express a M2 phenotype subsequently supporting tumor growth. How tumor cells polarize these TAMs to a pro-tumor M2 phenotype is still poorly understood. Our previous studies have revealed that a Toll-like receptor 2 (TLR2)-dependent autophagy triggered by hepatoma-derived factors down-regulates NF-κB p65 and drives M2 macrophage differentiation. However, the underlying mechanisms and potential hepatoma-derived TLR2 ligands are not clear. Here, we provide evidence to reveal that NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation is crucial for HCC-induced autophagy, NF-κB p65 down-regulation and M2 phenotype polarization in primary macrophages. This NOX2-generated ROS production in abolished in TLR2-deficient macrophages. HCC-derived or recombinant high-mobility group box 1 (HMGB1) is able to trigger this TLR2-mediated M2 macrophage polarization. Blockage of HMGB1 and ROS by inhibitors, ethyl pyruvate and N-acetylcysteine amide, respectively, significantly reduces both M2 macrophage accumulation and liver nodule formation in HCC-bearing mice. Our findings uncover a HMGB1/TLR2/NOX2/autophagy axis to trigger M2 macrophage polarization in HCC that can be considered as a novel therapeutic target for treating HCC.

Breast cancer is the most prevalent malignant neoplasm among women worldwide and in Taiwan, and the incidence of breast cancer has been increasing over the past years. Accumulating studies has shown that multiple stress responses are activated in breast cancer. Oncogene activation, massive proliferation and increased nutrient demands often result in nutrient and oxygen deprivation, which triggers integrated stress response (ISR) in tumor cells. ISR dictates the cellular adaptive signaling in response to the intrinsic and extrinsic stresses, which lead to endoplasmic reticulum (ER) stress and cytosolic stress. Delineating the regulatory mechanisms of ISR may help us understand how cancer cells adapt and survive under stressed condition. To elucidate the role of long non-coding RNAs (lncRNAs) in the ISR of breast cancer, we have performed a two-step human lncRNA RNA interference (RNAi) screening coupled with cell viability assays in a breast cancer cell line MDA-MB-231 under glucose deprivation to induce extrinsic metabolic stress. A novel lncRNA, UBA6-AS1, was identified to be upregulated to promote breast cancer cell death upon glucose deprivation. Besides of glucose deprivation, UBA6-AS1 was also induced by the deprivation of amino acids including glutamine and arginine in several breast cancer cell lines, suggesting that the upregulation of UBA6-AS1 was a universal metabolic stress event. We also found that UBA6-AS1 expression was increased upon the administration of ER stress inducers, tunicamycin (Tm) and thapsigargin (Tg) in breast cancer cells, implicating a potential role of UBA6-AS1 in harmonizing the nutrient and ER stresses. Moreover, after analyzing the genomic position and sequence of UBA6-AS1, activating transcription factor 4 (ATF4), a critical regulator in the ISR coordinating nutrient and ER stress signaling for controlling cell survival and stress adaption, has been predicted to be the regulator of UBA6-AS1 upon the induction of nutrient stress, further supporting the role of UBA6-AS1 participating in the ISR of breast cancer cells. Depletion of UBA6-AS1 rendered breast cancer cells more resistant to nutrient deprivation, and the opposite results were observed when UBA6-AS1 was overexpressed, indicating that UBA6-AS1 may participate in the regulation of breast cancer cell survival under metabolic stress. To investigate the function of UBA6-AS1, RNA-sequencing (RNA-seq) was performed to profile gene expression in breast cancer cells overexpressing UBA6-AS1. The RNA-seq analysis revealed that the top 10 enriched biological processes were mostly related to apoptosis or programmed cell death in the UBA6-AS1 overexpressing cells, suggesting that the up-regulation of UBA6-AS1 may induce apoptosis in response to metabolic stress. In the future, we will focus on the molecular mechanism of the regulation and function of UBA6-AS1 as well as its biological role and association with breast cancer progression. Citation Format: Yi-Zhen Wu, Yi-Hsuan Chen, Chun-Ting Cheng, Kevin Chi, Tse-Chun Kuo, Hsing-Jien Kung, David Kong Ann, Ching-Ying Kuo. lncRNA UBA6-AS1 participates in the integrated stress response of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-10.

Oncogene activation, massive proliferation, and increased nutrient demands often result in nutrient and oxygen deprivation in solid tumors including breast cancer (BC), leading to the induction of oxidative stress and endoplasmic reticulum (ER) stress, and subsequently triggering integrated stress response (ISR). To elucidate the role of long non-coding RNAs (lncRNAs) in the ISR of BC, we performed transcriptome analyses and identified a lncRNA, UBA6-AS1, which was upregulated upon amino acid deprivation and ER stress. UBA6-AS1 was preferentially induced in triple-negative BC (TNBC) cells deprived of arginine or glutamine, two critical amino acids required for cancer cell growth, or treated with ER stress inducers. Mechanistically, UBA6-AS1 was regulated through the GCN2/eIF2α/ATF4 pathway, one of the major routes mediating ISR in amino acid sensing. In addition, both in vitro and in vivo assays indicated that UBA6-AS1 promoted TNBC cell survival when cells encountered metabolic stress, implicating a regulatory role of UBA6-AS1 in response to intratumoral metabolic stress during tumor progression. Moreover, PARP1 expression and activity were positively regulated by the GCN2/UBA6-AS1 axis upon amino acid deprivation. In conclusion, our data suggest that UBA6-AS1 is a novel lncRNA regulating ISR upon metabolic stress induction to promote TNBC cell survival. Furthermore, the GCN2-ATF4 axis is important for UBA6-AS1 induction to enhance PARP1 activity and could serve as a marker for the susceptibility of PARP inhibitors in TNBC.

The formation of edges in 2D configured nanomaterials are special sites which possess different arrangements of atoms and properties compared to that of plain nanomaterials. Herein, a novel strategy is used to synthesize the self-assembled 2D configured edges with twisted building blocks of glucose reduced graphene oxide (grGO)-incorporated NiO-coated ZnO NRs via soft chemical route. It is envisioned that the present hierarchical nanostructures will stimulate the performances of UV photodetection due to these combinations of materials. The as-prepared samples such as ZnO nanorods (NRs), NiO-ZnO NRs, grGO-ZnO NRs and grGO-incorporated NiO-ZnO NRs are designed using Ag interdigitated electrodes. Remarkably, the as-fabricated grGO-incorporated NiO-ZnO NRs shows enhanced photodetection properties when compared to those of bare ZnO NRs, NiO-ZnO NRs and grGO-ZnO. Especially, the grGO-incorporated NiO-ZnO NRs photodetector exhibits the highest UV on/off ratio of 3 × 104 which is ~60 times better than that of bare ZnO NRs photodetector. The results reveal that the development of p-n junction along grGO coating at the surface of NiO-ZnO enhances the relaxation dynamics of ZnO NRs by reducing the photocarriers contact with O2 species due to surface passivation. The present grGO-NiO-ZnO photodetectors might opening up a new opportunities for future optoelectronic devices.

Rice (Oryza sativa L.) has two ecotypes, upland and lowland rice, that have been observed to show different tolerance levels under flooding stress. In this study, two rice cultivars, upland (Up221, flooding-intolerant) and lowland (Low88, flooding-tolerant), were initially used to study their molecular mechanisms in response to flooding germination. We observed that variations in the OsCBL10 promoter sequences in these two cultivars might contribute to this divergence in flooding tolerance. Further analysis using another eight rice cultivars revealed that the OsCBL10 promoter could be classified as either a flooding-tolerant type (T-type) or a flooding-intolerant type (I-type). The OsCBL10 T-type promoter only existed in japonica lowland cultivars, whereas the OsCBL10 I-type promoter existed in japonica upland, indica upland and indica lowland cultivars. Flooding-tolerant rice cultivars containing the OsCBL10 T-type promoter have shown lower Ca2+ flow and higher α-amylase activities in comparison to those in flooding-intolerant cultivars. Furthermore, the OsCBL10 overexpression lines were sensitive to both flooding and hypoxic treatments during rice germination with enhanced Ca2+ flow in comparison to wild-type. Subsequent findings also indicate that OsCBL10 may affect OsCIPK15 protein abundance and its downstream pathways. In summary, our results suggest that the adaptation to flooding stress during rice germination is associated with two different OsCBL10 promoters, which in turn affect OsCBL10 expression in different cultivars and negatively affect OsCIPK15 protein accumulation and its downstream cascade.

We conducted 3 laboratory experiments to determine how face consciousness influences consumption of counterfeit luxury goods, along with the moderating roles of usage occasion and brand prominence. The participants in the first study were 138 Chinese undergraduates who were allocated to a 2 × 2 design to evaluate their intention to purchase a counterfeit luxury item that would be used either in public or in private. In Studies 2 and 3, using two 2 × 2 designs we evaluated the purchase intention of the participants (132 and 136, respectively) in order to investigate the moderating role of brand prominence. The results showed that participants' face consciousness had a significant positive influence on intention to purchase counterfeit luxury goods. In addition, the products' usage occasion and brand prominence positively moderated the influence that face consciousness had on counterfeit luxury item purchase intention of our participant groups.

Objective The present study examined the relation between deja vu experiences and paranormal beliefs in schizophrenic patients. Methods A total of 522 participants (54.5% female; mean age = 33.3, SD = 16.02) were recruited, including 422 healthy adults (60.9% female; mean age = 29.48, SD = 15.07) and 100 medicated adult schizophrenic patients (27.3% female; mean age = 48.98, SD = 8.57). The Chinese version of the Inventory of Deja-vu Experiences Assessment was created via back translation. Chinese versions of the Revised Paranormal Belief Scale (CRPB), Beck Anxiety Inventory (CBAI), and Perceived Stress Scale (CPSS) were also used. Results and Conclusion After controlling for age, gender, education, and anxiety, the results supported the following three hypotheses. Schizophrenic persons have fewer deja vu experiences than normal persons. These experiences are positively related to paranormal beliefs in healthy adults but not in schizophrenic patients. Schizophrenic patients have higher scores than healthy adults on the psi and superstitious subscales of the CRPB.

High-performance InP/GaAsSb double heteroj unction bipolar transistor (DHBT) employing GaAsSb/lnGaAs superlattice-base structure is demonstrated and compared with GaAsSb bulk-base structure by two-dimensional simulation analysis. The proposed device exhibits a higher current gain of 257 than the conventional InP/GaAsSb type-II DHBT with a lower current gain of 180, attributed to the tynneling behavior of minority carriers in the GaAsSb/lnGaAs superlattice-base region under large forward base—emitter bias. In addition, a larger unity gain cutoff frequency of 19.1 GHz is botained for the superlattice-base device than that of 17.2 GHz for the bulk-base device.

In this paper, the device performance and complementary inverter of the InGaP/InGaAs/GaAs doped-channel field-effect transistors (DCFETs) by two-dimensional semiconductor simulation are demonstrated. Due to the relatively large conduction (valance) band discontinuity at InGaP/InGaAs interface, it provides good confinement effect for transporting carriers in InGaAs channel layer for the n-channel (p-channel) device. The large gate turn-on voltage is achieved due to the employment of the wide energy-gap InGaP material as gate layer. The f t and f max are of 6.5 (2.1) and 25 (5) GHz for the n-channel (p-channel) device. Furthermore, the co-integrated structures, by the combination of n- and p-channel field-effect transistors, could form a complementary inverter and the relatively large noise margins are achieved.

The characteristics of InGaP/GaAs heterostructure-emitter bipolar transistors (HEBTs) including conventional GaAs bulk base, InGaAs/GaAs superlattice-base, and InGaAs quantum-well base structures are presented and compared by two-dimensional simulation analysis. Among of the devices, the superlattice-base device exhibits a highest collector current, a highest current gain and a lowest base–emitter turn-on voltage attributed to the increased charge storage of minority carriers in the InGaAs/GaAs superlattice-base region by tunneling behavior. The relatively low turn-on voltage can reduce the operating voltage and collector–emitter offset voltage for low power consumption in circuit applications. However, as to the quantum-well base device, the electrons injecting into the InGaAs well are blocked by the p+-GaAs bulk base and it causes a great quantity of electron storage within the small energy-gap n-type GaAs emitter layer, which significantly increases the base recombination current as well as degrades the collector current and current gain.

In this article, a novel InGaP/GaAs pnp δ-doped heterojunction bipolar transistor is first demonstrated. Though the valence band discontinuity at InGaP/GaAs heterojunction is relatively large, the addition of a δ-doped sheet between two spacer layers at the emitter-base junction effectively eliminates the potential spike and increases the confined barrier for electrons, simultaneously. Experimentally, a high current gain of 25 and an offset voltage of 100 mV are achieved. The offset voltage is much smaller than the conventional InGaP/GaAs pnp HBT. The proposed device could be used for linear amplifiers and low-power complementary integrated circuit applications.