Isolation and Biological Evaluation of Alfa-Mangostin as Potential Therapeutic Agents against Liver Fibrosis.

The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-ß1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl4) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-ß1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl4-induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.

The effects of additive manufacturing technologies and finish line designs on the trueness and dimensional stability of 3D-printed dies.

PURPOSE: To evaluate the effects of 5 manufacturing technologies and 2 finish line designs on the trueness and dimensional stability of 3D-printed definitive dies at finish line regions under different storage conditions and time. MATERIAL AND METHODS: Preparation of light chamfer and round shoulder finish lines were adopted individually on two mandibular first molar typodont teeth and digitalized as standard tessellation language (STL) files. A total of 240 samples (192 AM definitive dies and 48 definitive conventional stone dies) in 20 groups (n = 12) were manufactured based on 2 finishing line designs (chamfer and shoulder), 5 manufacturing technologies (4 additively manufactured technologies and conventional stone die), and 2 storage conditions (light exposure and dark). The 4 additively manufactured (AM) technologies include a DLP 3D-printer, an economic LED 3D-printer, a CLIP 3D-printer, and an SLA 3D-printer. All the study samples were distributed into two storage conditions. Subsequently, samples were digitalized to STL files at 3 different time points (within 36 hours, 1-month, and 3-months). A surface matching software was used to superimpose the sample STL files onto the corresponding original STL files with the best-fit alignment function. The trueness of each printed and stone definitive dies and their dimensional stabilities were measured by the root mean square (RMS, in mm). A linear mixed-effects model was used to test the effects of the finish line design, manufacturing technology, storage condition, and storage time on RMS values (α = 0.05). RESULTS: While finish line designs had no significant effects [F(1, 220) = 0.85, p < 0.358], the manufacturing technologies [F(3, 220) = 33.02, p < 0.001], storage condition [F(1, 220) = 4.11, p = 0.044], and storage time F(2, 440) = 10.37, p < 0.001] affected the trueness and dimensional stability of 3D-printed dies at finish line regions. No significant interactions were found among the 4 factors. For the manufacturing technologies, Type IV stone groups and LCD 3D-printer groups had significantly higher RMS values than the other 3 printers (p < 0.001) with no significant differences between Type IV stone and LCD 3D-printer groups (p = 0.577). DLP 3D-printer groups had higher RMS values than both SLA 3D-printer groups and CLIP 3D-printer groups (p < 0.001). There were no significant differences between SLA 3D-printer groups and CLIP 3D-printer groups, p = 0.671. For the effects of storage conditions, RMS values were significantly higher in the groups stored with the direct light exposure than the ones stored in the dark, p = 0.044. In terms of the effects of storage time, the RMS values were significantly higher after 1-month storage, p = 0.002; and 3-month storage, p < 0.001, than the ones at the immediate postmanufacturing stage. However, the RMS values after 1-month and 3-month storage were not significantly different from each other (p = 0.169). CONCLUSIONS: Manufacturing technologies, storage conditions, and storage time significantly affected the trueness and dimensional stability of 3D-printed dies at finish line regions, while finish line designs had no significant effects. Among the AM technologies tested, all have produced either comparable or truer 3D-printed dies than the Type IV dental stone dies, and the CLIP and SLA 3D-printers produced the best outcomes. 3D-printed dies showed significant distortion after 1-month and 3-months storage, especially under light exposure storage conditions. These findings may negate the clinical need to preserve 3D-printed dies, and digital data should be preserved instead.

Nanoscale-cavity enhancement of color conversion with colloidal quantum dots embedded in the surface nano-holes of a blue-emitting light-emitting diode.

Although the method of inserting colloidal quantum dots (QDs) into deep nano-holes fabricated on the top surface of a light-emitting diode (LED) has been widely used for producing effective Förster resonance energy transfer (FRET) from the LED quantum wells (QWs) into the QDs to enhance the color conversion efficiency, an important mechanism for enhancing energy transfer in such an LED structure was overlooked. This mechanism, namely, the nanoscale-cavity effect, represents a near-field Purcell effect and plays a crucially important role in enhancing the color conversion efficiency. Here, we demonstrate the results of LED performance, time-resolved photoluminescence (TRPL), and numerical simulation to elucidate the nanoscale-cavity effect on color conversion by inserting a photoresist solution of red-emitting QDs into the nano-holes fabricated on a blue-emitting QW LED. Based on the TRPL study of the inserted QDs in a nano-hole structure fabricated on an un-doped GaN template of no QW, it is found that the emission efficiency of the inserted QDs is significantly increased due to the nanoscale-cavity effect. From the simulation study, it is confirmed that this effect can also increase the FRET efficiency, particularly for those radiating dipoles in the QWs oriented perpendicular to the sidewalls of the nano-holes. In the nanoscale-cavity effect, the enhanced near field distribution inside a nano-hole excited by a light emitter modifies its own radiation behavior through the Purcell effect such that its far-field emission becomes stronger.

CD44 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the fourth leading cause of male cancer death in Taiwan. Exposure to environmental carcinogens is the primary risk factor for developing OSCC. CD44, a well-known tumor marker, plays a crucial role in tumor cell differentiation, invasion, and metastasis. This study investigated CD44 single-nucleotide polymorphisms (SNPs) with environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Real-time polymerase chain reaction (PCR) was used to analyze 6 SNPs of CD44 in 599 patients with oral cancer and 561 cancer-free controls. We determined that the CD44 rs187115 polymorphism carriers with the genotype AG, GG, or AG+GG were associated with oral cancer susceptibility. Among 731 smokers, CD44 polymorphisms carriers with the betel-nut chewing habit had a 10.30-37.63-fold greater risk of having oral cancer compared to CD44 wild-type (WT) carriers without the betel-nut chewing habit. Among 552 betel-nut chewers, CD44 polymorphisms carriers who smoked had a 4.23-16.11-fold greater risk of having oral cancer compared to those who carried the WT but did not smoke. Finally, we also observed that the stage III and IV oral cancer patients had higher frequencies of CD44 rs187115 polymorphisms with the variant genotype (AG+GG) compared with the wild-type (WT) carriers. CONCLUSION: Our results suggest that gene-environment interactions between the CD44 polymorphisms and betel quid chewing and tobacco smoking increase the susceptibility to oral cancer development. Patients with CD44 rs187115 variant genotypes (AG+GG) were correlated with a higher risk of oral cancer development, and these patients may possess greater chemoresistance to advanced- to late-stage oral cancer than WT carriers do. The CD44 rs187115 polymorphism has potential predictive significance in oral carcinogenesis and also may be applied as factors to predict the clinical stage in OSCC patients.

CMOS compatible integration of Si/SiO2 multilayer GRIN lens optical mode size converter to Si wire waveguide.

We present a CMOS compatible mass manufacturable, compact Si/SiO(2) multilayer GRIN lens mode size converter from standard single mode fiber to 300 nm-thick Si waveguide. The fiber-to-GRIN lens coupling loss is 2.6 ± 0.3 dB (coupling efficiency: 51~60%) with optimized focal length of 11.6~11.8 µm and Si/SiO(2) multilayer thickness of 7.4 µm.

Ultra-compact multilayer Si/SiO(2) GRIN lens mode-size converter for coupling single-mode fiber to Si-wire waveguide.

We report on the fabrication and experimental demonstration of optical mode size transformation between standard single-mode fiber and 0.26 µm-thick Si-waveguide by 12 µm-thick Si/SiO(2) multilayer on-chip GRIN lens of lengths 16 µm or 24 µm butt-joint to 10 µm-wide terminated Si-waveguide. The overall coupling loss of the coupler was measured to be 3.45 dB in which the Fresnel reflection loss is estimated to be 2dB at the GRIN-lens/air interface. The on-chip integrated GRIN lens opens up the feasibility of a low cost passive aligned fiber-pigtailed electronic-photonics integrated circuits platform.