IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1.

T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.

Development of a titanium dioxide-assisted preconcentration/on-site vapor-generation chip hyphenated with inductively coupled plasma-mass spectrometry for online determination of mercuric ions in urine samples.

In this study, a novel automatic analytical methodology using a titanium dioxide (TiO2)-assisted preconcentration/on-site vapor-generation (VG) chip hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS) for online determination of mercuric ions (Hg2+) was developed. Interestingly, the TiO2 nanoparticle (nano-TiO2) coating on the channel surface acted not only as a sorbent for preconcentration but also as a catalyst for photocatalyst-assisted VG. Under optimum operation conditions, the developed method was validated by analyzing the certified reference material (CRM) Seronorm™ Trace Elements Urine L-2 (freeze-dried human urine). Based on the obtained results, the dramatic reduction of "hands-on" manipulation and the elimination of hazardous materials (e.g., sodium borohydride (NaBH4) and stannous chloride (SnCl2)) from the process enabled a simple and ultraclean procedure with an extremely low detection limit of 0.75 ng L-1 for Hg2+ in urine samples. To the best of our knowledge, this is the first study to report the direct exploitation of a nano-TiO2-coated microfluidic device for online sample preconcentration and on-site VG prior to ICP-MS measurement.

Rapid analysis of traditional Chinese medicine Pinellia ternata by microchip electrophoresis with electrochemical detection.

Traditional Chinese herbal medicine has long enjoyed the reputation of the world's most advanced system of natural medicine. Pinellia ternata is one of the most commonly used herbs in the traditional Chinese medical science. In this study, five representative ingredients of Pinellia ternata guanosine, methionine, glycine, 3,4-dihydroxybenzaldehyde, and homogentisic acid, were assayed using simple derivatization procedures. Under optimized experimental condition, five analytes in Pinellia ternata were rapidly separated and detected using microchip electrophoresis, affording the benefits of speed, minimal sample requirements, and sensitive on-the-chip electrochemical detection, in 5 min with linearity over a concentration of 20-500 µM (R2  = 0.994) with nearly complete recovery (95.6-98.5%).

Nanocomposite-Coated Microfluidic-Based Photocatalyst-Assisted Reduction Device To Couple High-Performance Liquid Chromatography and Inductively Coupled Plasma-Mass Spectrometry for Online Determination of Inorganic Arsenic Species in Natural Water.

To selectively and sensitively determine the trace inorganic As species, As(III) and As(V), we developed a nanocomposite-coated microfluidic-based photocatalyst-assisted reduction device (PCARD) as a vapor generation (VG) device to couple high-performance liquid chromatography (HPLC) separation and inductively coupled plasma-mass spectrometry (ICPMS) detection. Au nanoparticles were deposited on TiO2 nanoparticles to strengthen the conversion efficiency of the nanocomposite photocatalytic reduction. The sensitivity for As was significantly enhanced by employing the nanocomposite photocatalyst and using prereduction and signal-enhancement reagents. Under the optimal operating conditions, the analytical detection limits (based on 3σ) of the proposed online HPLC/nanocomposite-coated microfluidic-based PCARD/ICPMS system for As(III) and As(V) were 0.23 and 0.34 µg·L-1, respectively. The results were validated using a certified reference material (NIST SRM 1643e) and groundwater sample analysis, indicating the good reliability and applicability of our proposed system for the determination of inorganic As species in natural fresh water.

A high-throughput solid-phase extraction microchip combined with inductively coupled plasma-mass spectrometry for rapid determination of trace heavy metals in natural water.

Herein, a hyphenated system combining a high-throughput solid-phase extraction (htSPE) microchip with inductively coupled plasma-mass spectrometry (ICP-MS) for rapid determination of trace heavy metals was developed. Rather than performing multiple analyses in parallel for the enhancement of analytical throughput, we improved the processing speed for individual samples by increasing the operation flow rate during SPE procedures. To this end, an innovative device combining a micromixer and a multi-channeled extraction unit was designed. Furthermore, a programmable valve manifold was used to interface the developed microchip and ICP-MS instrumentation in order to fully automate the system, leading to a dramatic reduction in operation time and human error. Under the optimized operation conditions for the established system, detection limits of 1.64-42.54 ng L(-1) for the analyte ions were achieved. Validation procedures demonstrated that the developed method could be satisfactorily applied to the determination of trace heavy metals in natural water. Each analysis could be readily accomplished within just 186 s using the established system. This represents, to the best of our knowledge, an unprecedented speed for the analysis of trace heavy metal ions.

Are normal decision-makers sensitive to changes in value contrast under uncertainty? Evidence from the Iowa Gambling Task.

The Iowa Gambling Task (IGT) developed by Bechara et al. in 1994 is used to diagnose patients with Ventromedial Medial Prefrontal Cortex (VMPFC) lesions, and it has become a landmark in research on decision making. According to Bechara et al., the manipulation of progressive increments of monetary value can normalize the performance of patients with VMPFC lesions; thus, they developed a computerized version of the IGT. However, the empirical results showed that patients' performances did not improve as a result of this manipulation, which suggested that patients with VMPFC lesions performed myopically for future consequences. Using the original version of the IGT, some IGT studies have demonstrated that increments of monetary value significantly influence the performance of normal subjects in the IGT. However, other research has resulted in inconsistent findings. In this study, we used the computerized IGT (1X-IGT) and manipulated the value contrast of progressive increments (i.e., by designing the 10X-IGT, which contained 10 times of progressive increment) to investigate the influence of value contrast on the performance of normal subjects. The resulting empirical observations indicated that the value contrast (1X- vs. 10X-IGT) of the progressive increment had no effect on the performance of normal subjects. This study also provides a discussion of the issue of value in IGT-related studies. Moreover, we found the "prominent deck B phenomenon" in both versions of the IGT, which indicated that the normal subjects were guided mostly by the gain-loss frequency, rather than by the monetary value contrast. In sum, the behavioral performance of normal subjects demonstrated a low correlation with changes in monetary value, even in the 10X-IGT.