A Comprehensive Study of a Micro-Channel Heat Sink Using Integrated Thin-Film Temperature Sensors.

A micro-channel heat sink is a promising cooling method for high power integrated circuits (IC). However, the understanding of such a micro-channel device is not sufficient, because the tools for studying it are very limited. The details inside the micro-channels are not readily available. In this letter, a micro-channel heat sink is comprehensively studied using the integrated temperature sensors. The highly sensitive thin film temperature sensors can accurately monitor the temperature change in the micro-channel in real time. The outstanding heat dissipation performance of the micro-channel heat sink is proven in terms of maximum temperature, cooling speed and heat resistance. The temperature profile along the micro-channel is extracted, and even small temperature perturbations can be detected. The heat source formed temperature peak shifts towards the flow direction with the increasing flow rate. However, the temperature non-uniformity is independent of flow rate, but solely dependent on the heating power. Specific designs for minimizing the temperature non-uniformity are necessary. In addition, the experimental results from the integrated temperature sensors match the simulation results well. This can be used to directly verify the modeling results, helping to build a convincing simulation model. The integrated sensor could be a powerful tool for studying the micro-channel based heat sink.

Canonical and non-canonical Wnt signaling control the regeneration of amputated rodent vibrissae follicles.

Although mammals are notoriously poor at regeneration compared with many lower-order species, the hair follicle, particular to mammals, is capable of regeneration following partial amputation. The detailed internal mechanism of this phenomenon is still unclear. Development and regrowth of the hair follicle depends on dermal-epidermal interaction within the hair follicle. Previous studies have shown that Wnt/ß-catenin, Shh, Bmp, PDGF, TGF and Notch signals all take part in the development and growth of the hair follicle, and the Wnt/ß-catenin signaling additionally plays an indispensable role in hair follicle morphogenesis and regrowth. In this study, we investigated the localization, as well as, protein levels of Wnt/ß-catenin signaling molecules during amputated whisker follicle regeneration.

Comparisons between small intestinal and gastric feeding in severe traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials.

OBJECT: Nutritional support is highly recommended for reducing the risk of nosocomial infections, such as pneumonitis, in patients with severe traumatic brain injury (TBI). Currently, there is no consensus for the preferred route of feeding. The authors compared the risks of pneumonitis and other important outcomes associated with small intestinal and gastric feeding in patients with severe TBI. METHODS: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant randomized controlled trials (up to December 16, 2013) that compared small bowel to gastric feeding in patients with severe TBI were identified from searches in the PubMed and Embase databases. The primary outcome was risk of pneumonia. Secondary outcomes included ventilator-associated pneumonia, mortality, length of intensive care unit stay, length of hospital stay, duration of mechanical ventilation, total number of complications, aspiration, diarrhea, distention, Glasgow Coma Scale score, Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II score. RESULTS: Five randomized controlled trials with 325 participants in total were included in the meta-analysis. Compared with gastric feeding, small bowel feeding was associated with a significant reduction in the incidence of pneumonitis (risk ratio [RR] 0.67; 95% CI 0.52-0.87; p=0.002; I2=0.0%) and ventilator-associated pneumonia (RR 0.52; 95% CI 0.34-0.81; p=0.003; I2=0.0%). Small intestinal feeding was also associated with a decrease in the total number of complications (RR 0.43; 95% CI 0.20-0.93; p=0.03; I2=68%). However, small intestinal feeding did not seem to significantly convert any of the other end points in the meta-analysis. CONCLUSIONS: The limited evidence suggests that small bowel feeding in patients with severe TBI is associated with a risk of pneumonia that is lower than that with gastric feeding. From this result, the authors recommend the use of small intestinal feeding to reduce the incidence of pneumonitis in patients with severe TBI.

Expression of Wnt/ß-catenin signaling, stem-cell markers and proliferating cell markers in rat whisker hair follicles.

The rat whisker hair follicle (HF) is a model for studying the reconstruction of the HF or dermal papilla (DP), and involves the Wnt/ß-catenin signaling pathway, which is a key pathway in HF development and HF cycling after birth. It has been reported that Wnt/catenin signaling plays an indispensable role in human or rat pelages development and postnatal growth. However, the distribution of some Wnt/ß-catenin signaling pathway factors and their relationship with the epithelial stem cell markers in whisker follicles has not been characterized. In this study, we investigated the immunolocalization of Wnt/catenin signaling pathway members, including Wnt10b, Wnt10a, Wnt5a, ß-catenin, and downstream lymphoid enhancer-binding factor 1 (LEF1) and transcription factor 3 (TCF3), as well as, HF stem-cell markers CD34, CK15 and proliferating cell nuclear antigen (PCNA) protein, in rat anagen phase whisker follicles. ß-catenin, Wnt5a, Wnt10b, Wnt10a, LEF1, and TCF3 were expressed in the outer root sheath (ORS), inner root sheath, matrix and hair shaft of anagen follicles. ß-catenin, Wnt10b, LEF1, and TCF3 were highly expressed and Wnt5a and Wnt10a weakly expressed in DP and dermal sheath (DS) regions. The expression of α-smooth muscle actin was strong in the lower DS and it was also detected in some DP cells. CD34, CK15 and PCNA were all expressed in the ORS; and CD34 and PCNA were also detected in the matrix, however CD34 was extensively expressed in DP and DS regions. Our studies located the position of Wnts, downstream LEF1 and TCF3 and stem cell marker proteins, which provide new information in understanding the role of the Wnt singaling pathway in whisker follicles' growth.

Long noncoding RNA expression in dermal papilla cells contributes to hairy gene regulation.

Dermal papilla (DP) cells may be the source of dermal-derived signaling molecules involved in hair-follicle development and postnatal hair cycling. Early-passage DP cells can induce hair growth in vivo, but, on further culture, this ability is lost. The cellular mechanisms underlying the hair-follicle induction property of early-passage DP cells are unclear. Long noncoding RNAs (lncRNAs) are an important class of genes involved in various biological functions. They are aberrantly expressed and play roles in the regulation of the Wnt signaling pathway, a critical point in maintaining hair-induction activity. LncRNA microarray revealed 1683 upregulated and 1773 downregulated lncRNAs in passage-4 DP cells compare with passage-10 DP cells. To investigate the relation between lncRNAs and coding genes in WNT signaling, we constructed a coding-noncoding gene co-expression network using lncRNAs and coding genes that were differentially expressed between the passage-4 and -10 DP cells. RP11-766N7.3, H19 and HOTAIR are specific lncRNAs that were aberrantly expressed in DP cells and played an important role in regulating Wnt signaling. This study may provide potential targets for discovering the hair-follicle induction mechanism of early-passage DP cells.

Expression of estrogen receptor α and ß in esophageal squamous cell carcinoma.

Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ERα and ERß expression levels. Our results showed that ERα immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ERß status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ERα expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ERα and ERß in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERα expression (21/89) had a better outcome than patients without ERα expression (P=0.0280), whereas patients with high ERß immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ERα and ERß levels were inversely correlated, and the downregulation of ERα and upregulation of ERß may indicate unfavorable prognosis of ESCC.

Human papillomavirus type 18 E6 and E7 genes integrate into human hepatoma derived cell line Hep G2.

BACKGROUND AND OBJECTIVES: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. METHODS: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. RESULTS: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. CONCLUSION: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study.

A simple, noninvasive and efficient method for transdermal delivery of siRNA.

Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell-cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy.

Characterization of apoptosis and proliferation in esophageal carcinoma EC109 cells following siRNA-induced down-regulation of TRAF6.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an activator of the NF-κB transcription factor. NF-κB is involved in a variety of inflammatory, anti-apoptotic, and gene regulatory pathways and was recently found to be over-expressed in esophageal cancer cells. Here we investigated the function of TRAF6 in the esophageal cancer cell line EC109. siRNA targeting TRAF6 was introduced into EC109 cells and TRAF6 mRNA and protein levels were subsequently examined via RT-PCR and western blotting. Rates of apoptosis and cell proliferation were also measured using flow cytometry, ethynyl deoxyuridine (EdU), and CCK-8 (Cell Counting Kit-8) assays. The real-time PCR array was applied to profile the expression of TRAF6 related genes. TRAF6-siRNA reduced TRAF6 mRNA and protein expressions. NF-κB p65 protein expression was decreased in TRAF6-targeting siRNA-transfected cells compared to cells of the negative control. TRAF6-siRNA also significantly inhibited proliferation and enhanced apoptosis of EC109 cells. These studies suggested that TRAF6 was required for NF-κB activation in EC109 cells and it may be a good molecular target for suppressing the survival and proliferation of esophageal cancer cells.