Parallel probing of drug uptake of single cancer cells on a microfluidic device

Drug resistance is frequently developing during treatment of cancer patients. Intracellular drug uptake is one of the important characteristics to understand mechanism of drug resistance. However, the heterogeneity of cancer cells requires the investigation of drug uptake at the single cell level. Here, we developed a microfluidic device for parallel probing of drug uptake. We combined a v-type valve and peristaltic pumping to select individual cells from a pool of prostate cancer cells (PC3) and place them successively in separate cell chambers in which they were exposed to the drug. Six different concentrations of doxorubicin, a naturally fluorescent anti-cancer drug, were created in loop-shaped reactors and exposed to the cell in closed 2 nL volume chambers. Monitoring every single cell over time in 18 parallel chambers revealed increased intracellular fluorescence intensity according to the dose of doxorubicin, as well as nuclear localization of the fluorescent drug after 2 h of incubation. The herein proposed technology demonstrated a first series of proof of concept experiments and it shows high potential to use for probing drug sensitivity of single cancer cell

Fipronil Promotes Adipogenesis via AMPKα-mediated Pathway in 3T3-L1 Adipocytes

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10 mM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The activation of AMPKα with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) abolished effects of fipronil on increased adipogenesis. These results suggest that fipronil alters adipogenesis and results in increased lipid accumulation through a AMPKα-mediated pathway

CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1.

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson\u27s disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1(-/-) mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP(+))-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling

Embracing Limited and Imperfect Data: A Review on Plant Stress Recognition Using Deep Learning

Plant stress recognition has witnessed significant improvements in recent years with the advent of deep learning. A large-scale and annotated training dataset is required to achieve decent performance; however, collecting it is frequently difficult and expensive. Therefore, deploying current deep learning-based methods in real-world applications may suffer primarily from limited and imperfect data. Embracing them is a promising strategy that has not received sufficient attention. From this perspective, a systematic survey was conducted in this study, with the ultimate objective of monitoring plant growth by implementing deep learning, which frees humans and potentially reduces the resultant losses from plant stress. We believe that our paper has highlighted the importance of embracing this limited and imperfect data and enhanced its relevant understanding

Hepatic Metastasis from Choriocarcinoma: Angiographic Findings in Two Cases

We report two cases of hepatic metastases from choriocarcinoma in women of childbearing age in whom imaging studies performed at presentation revealed the presence of liver masses, and who had clinically progressive anemia or intraabdominal hemorrhage. CT demonstrated heterogeneously enhanced liver masses. Characteristic angiographic findings included hypervascular hepatic masses with aneurysmal dilatations of the peripheral hepatic arteries at the arterial phase and persistent vascular lakes at the venous phase

Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate.

Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 mutation are among the most frequently observed alterations in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there are no biologically relevant models that can be used to assess the molecular mechanisms for these genetic abnormalities. Here, we report a novel mouse model, in which elevated transgenic AR expression and Trp53 deletion occur simultaneously in mouse prostatic epithelium to mimic human prostate cancer cells. These compound mice developed an earlier onset of high-grade prostatic intraepithelial neoplasia and accelerated prostate tumors in comparison with mice harboring only the AR transgene. Histological analysis showed prostatic sarcomatoid and basaloid carcinomas with massive squamous differentiation in the above compound mice. RNA-sequencing analyses identified a robust enrichment of the signature genes for human prostatic basal cell carcinomas in the above prostate tumors. Master regulator analysis revealed SOX2 as a transcriptional regulator in prostatic basal cell tumors. Elevated expression of SOX2 and its downstream target genes were detected in prostatic tumors of the compound mice. Chromatin immunoprecipitation analyses implicate a coregulatory role of AR and SOX2 in the expression of prostatic basal cell signature genes. Our data demonstrate a critical role of SOX2 in prostate tumorigenesis and provide mechanistic insight into prostate tumor aggressiveness and progression mediated by aberrant AR and p53 signaling pathways

High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation

Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated

Impacts of Heavy Rain and Typhoon on Allergic Disease

AbstractObjectivesAllergic disease may be increased by climate change. Recent reports have shown that typhoon and heavy rain increase allergic disease locally by concentration of airborne allergens of pollen, ozone, and fungus, which are causes of allergic disease. The objective of this study was to determine whether typhoon and heavy rain increase allergic disease in Korea.MethodsThis study included allergic disease patients of the area declared as a special disaster zone due to storms and heavy rains from 2003 to 2009. The study used information from the Korea Meteorological Administration, and from the National Health Insurance Service for allergic diseases (asthma, allergic rhinitis, and atopic dermatitis).ResultsDuring a storm period, the numbers of allergy rhinitis and atopic dermatitis outpatients increased [rate ratio (RR) = 1.191; range, 1.150–1.232] on the sixth lag day. However, the number of asthma outpatients decreased (RR = 0.900; range, 0.862–0.937) on the sixth lag day after a disaster period. During a storm period, the numbers of allergic rhinitis outpatients (RR = 1.075; range, 1.018–1.132) and atopy outpatients increased (RR = 1.134; range, 1.113–1.155) on the seventh lag day. However, the number of asthma outpatients decreased to RR value of 0.968 (range, 0.902–1.035) on the fifth lag day.ConclusionThis study suggests that typhoon and heavy rain increase allergic disease apart from asthma. More study is needed to explain the decrease in asthma