Nematicidal Activity of Grammicin Biosynthesis Pathway Intermediates in Xylaria grammica KCTC 13121BP against Meloidogyne incognita.

Grammicin, a polyketide metabolite produced by the endolichenic fungus Xylaria grammica KCTC 13121BP, shows strong nematicidal activity against Meloidogyne incognita. This study was performed to elucidate the grammicin biosynthesis pathway of X. grammica KCTC 13121BP and to examine the nematicidal activity of the biosynthesis intermediates and derivatives against M. incognita. Two grammicin biosynthesis intermediates were isolated from a T-DNA insertion transformant (strain TR-74) of X. grammica KCTC 13121BP and identified as 2-(hydroxymethyl)cyclohexa-2,5-diene-1,4-dione (compound 1) and 2,5-dihydroxybenzaldehyde (compound 2), which were also reported to be intermediates in the biosynthesis pathway of patulin, an isomer of grammicin. This indicates that the grammicin biosynthesis pathway overlaps almost with that of patulin, except for the last few steps. Among 13 grammicin biosynthesis intermediates and their derivatives (except grammicin), toluquinol caused the highest M. incognita J2 mortality, with an LC50/72 h value of 11.13 µg/mL, which is similar to grammicin with an LC50/72 h value of 15.95 µg/mL. In tomato pot experiments, the wettable powder type formulations (WP) of toluquinol (17.78 µg/mL) and grammicin (17.78 µg/mL) also effectively reduced gall formation on the roots of tomato plants with control values of 72.22% and 77.76%, respectively, which are much higher than abamectin (16.67%), but lower than fosthiazate (100%). The results suggest that toluquinol can be used directly as a biochemical nematicide or as a lead molecule for the development of new synthetic nematicides for the control of root-knot nematode diseases.

A Single-Chip 64-Channel Ultrasound RX-Beamformer Including Analog Front-End and an LUT for Non-Uniform ADC-Sample-Clock Generation.

A 64-channel RX digital beamformer was implemented in a single chip for 3-D ultrasound medical imaging using 2-D phased-array transducers. The RX beamformer chip includes 64 analog front-end branches including 64 non-uniform sampling ADCs, a FIFO/Adder, and an on-chip look-up table (LUT). The LUT stores the information on the rising edge timing of the non-uniform ADC sampling clocks. To include the LUT inside the beamformer chip, the LUT size was reduced by around 240 times by approximating an ADC-sample-time profile w.r.t. focal points (FP) along a scanline (SL) for a channel into a piece-wise linear form. The maximum error between the approximated and accurate sample times of ADC is eight times the sample time resolution (Ts) that is 1/32 of the ultrasound signal period in this work. The non-uniform sampling reduces the FIFO size required for digital beamforming by around 20 times. By applying a 9-dot image from Field-II program and 2-D ultrasound phantom images to the fabricated RX beamformer chip, the original images were successfully reconstructed from the measured output. The chip in a 0.13-um CMOS occupies 30.25 [Formula: see text] and consumes 605 mW.

A single-chip 32-channel analog beamformer with 4-ns delay resolution and 768-ns maximum delay range for ultrasound medical imaging with a linear array transducer.

A single-chip 32-channel analog beamformer is proposed. It achieves a delay resolution of 4 ns and a maximum delay range of 768 ns. It has a focal-point based architecture, which consists of 7 sub-analog beamformers (sub-ABF). Each sub-ABF performs a RX focusing operation for a single focal point. Seven sub-ABFs perform a time-interleaving operation to achieve the maximum delay range of 768 ns. Phase interpolators are used in sub-ABFs to generate sampling clocks with the delay resolution of 4 ns from a low frequency system clock of 5 MHz. Each sub-ABF samples 32 echo signals at different times into sampling capacitors, which work as analog memory cells. The sampled 32 echo signals of each sub-ABF are originated from one target focal point at one instance. They are summed at one instance in a sub-ABF to perform the RX focusing for the target focal point. The proposed ABF chip has been fabricated in a 0.13- µ m CMOS process with an active area of 16 mm (2). The total power consumption is 287 mW. In measurement, the digital echo signals from a commercial ultrasound medical imaging machine were applied to the fabricated chip through commercial DAC chips. Due to the speed limitation of the DAC chips, the delay resolution was relaxed to 10 ns for the real-time measurement. A linear array transducer with no steering operation is used in this work.

An analog-digital hybrid RX beamformer chip with non-uniform sampling for ultrasound medical imaging with 2D CMUT array.

To reduce the memory area, a two-stage RX beamformer (BF) chip with 64 channels is proposed for the ultrasound medical imaging with a 2D CMUT array. The chip retrieved successfully two B-mode phantom images with a steering angle from -45 (°) to +45 (°), the maximum delay range of 8 µs, and the delay resolution of 6.25 ns. An analog-digital hybrid BF (HBF) is chosen for the proposed chip to utilize the easy beamforming operation in the digital domain and also to reduce chip area by minimizing the number of ADCs. The chip consists of eight analog beamformers (ABF) for the 1st-stage and a digital beamformer (DBF) for the 2nd-stage. The two-stage architecture reduces the memory area of both ABF and DBF by around four times. The DBF circuit is divided into three steps to further reduce the digital FIFO memory area by around twice. Coupled with the non-uniform sampling scheme, the proposed two-stage HBF chip reduces the total memory area by around 40 times compared to the uniform-sampling single-stage BF chip. The chip fabricated in a 0.13- µm CMOS process occupies the area of 19.4 mm(2), and dissipates 1.14 W with the analog supply of 3.3 V and the digital supply of 1.2 V.

Increased expression of cathelicidin by direct activation of protease-activated receptor 2: possible implications on the pathogenesis of rosacea.

PURPOSE: Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. MATERIALS AND METHODS: Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). RESULTS: Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment. CONCLUSION: PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin.

Biological activities of fusarochromanone: a potent anti-cancer agent.

BACKGROUND: Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. RESULTS: Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 µM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. CONCLUSIONS: Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

Protease-activated receptor-2 activates NQO-1 via Nrf2 stabilization in keratinocytes.

BACKGROUND: Protease-activated receptor-2 (PAR-2) mediates inflammation and immune responses by serine proteinases. NF-E2-related factor 2 (Nrf2) confers protection against tissue injury through antioxidant responses to oxidative stress induced by a variety of factors, including electrophilic chemicals, hydrogen peroxide, and ultraviolet irradiation. OBJECTIVE: In this study, we investigated if PAR-2 activation can stimulate Nrf2 signaling to preserve homeostasis in keratinocytes. METHODS: We performed western blotting, real-time reverse transcription polymerase chain reaction, and immunocytochemistry of keratinocyte cultures, as well as immunohistochemical labeling of human skin samples. Short interfering RNA (siRNA) was employed to confirm the effects of PAR-2 activation. RESULTS: PAR-2 activation with a selective PAR-2 agonist peptide increased the nuclear level of Nrf2 protein and subsequently induced phase II enzyme expression. Nrf2 signaling via PAR-2 activation was confirmed with experiments using PAR-2-siRNA-treated keratinocytes. The activation of an Nrf2-targeted gene by PAR-2 activation was not induced by new production of Nrf2 but by prolonged stabilization of Nrf2. Lesional skin samples from vitiligo patients showed significantly lower expression of PAR-2 and Nrf2 than control skin samples. CONCLUSION: Collectively, PAR-2 activation enhanced nuclear Nrf2 translocation, and PAR-2-mediated Nrf2 activation was attributable to existing Nrf2 stabilization rather than de novo production. Our findings suggest that in addition to induction of inflammation, PAR-2 can play a chemopreventative role via Nrf2 stabilization in keratinocytes.

Efficacy and safety of 1,064 nm Q-switched Nd:YAG laser treatment for removing melanocytic nevi.

BACKGROUND: Until recently, the removal of melanocytic nevi has been performed with a CO(2) laser or Er:YAG laser. These lasers have been useful for removing affected spots. However, enlargement of spots or some sequelae, including depressed or hypertrophic scars, could develop as unwanted results. The Q-switched Nd:YAG laser has been used to remove deep-seated melanocytes, such as Ota nevus or tattoos. However, there have been no previous experiments performed to test the efficacy and safety of this laser treatment for melanocytic nevi. OBJECTIVE: The objective of this study was to investigate the efficacy and safety of the 1,064 nm Q-switched Nd:YAG laser for removing melanocytic nevi, including congenital nevomelanocytic and acquired nevomelanocytic nevi. METHODS: Two thousand and sixty four Korean patients with small melanocytic nevi were treated with a Q-switched Nd:YAG laser from 2005 to 2009. High-resolution photographs were taken in identical lighting and positions before and after the six weeks of treatment to observe the procedural efficacy. RESULTS: About 70% of the nevi treated using a 1,064 nm Q-switched Nd:YAG laser were completely removed after one session. The other 30% were completely treated within three sessions. The appearance of sequelae such as hollow scars noticeably decreased compared to the results seen in CO(2) or Er:YAG laser treatments. CONCLUSION: Use of the 1,064 nm Q-switched Nd:YAG laser is a safe and effective treatment modality for melanocytic nevi.

Childhood granulomatous periorificial dermatitis.

Childhood granulomatous periorificial dermatitis (CGPD), also known as facial Afro-Caribbean childhood eruption (FACE), is a distinctive granulomatous form of perioral dermatitis. It is a condition of unknown etiology, characterized by monomorphous, small, papular eruptions around the mouth, nose and eyes that histopathologically show a granulomatous pattern. It affects prepubescent children of both sexes and typically persists for several months but resolved without scarring. We report a 9 year-old girl with multiple, discrete, monomorphic, papular eruptions of 2-months duration on the perioral and periocular areas. Histopathological examination demonstrated upper dermal and perifollicular granulomatous infiltrate.