4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial ß-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.

Enhanced electrical properties of amorphous In-Sn-Zn oxides through heterostructuring with Bi2Se3 topological insulators.

Amorphous indium tin zinc oxide (a-ITZO)/Bi2Se3 nanoplatelets (NPs) were fabricated using a two-step procedure. First, Bi2Se3 NPs were synthesized through thermal chemical vapor deposition at 600 °C on a glass substrate, and then a-ITZO was deposited on the surface of the Bi2Se3 NPs via magnetron sputtering at room-temperature. The crystal structures of the a-ITZO/Bi2Se3 NPs were determined via X-ray diffraction spectroscopy and high-resolution transmission electron microscopy. The elemental vibration modes and binding energies were measured using Raman spectroscopy and X-ray photoelectron spectroscopy. The morphologies were examined using field-emission scanning electron microscopy. The electrical properties of the a-ITZO/Bi2Se3 NPs were evaluated using Hall effect measurements. The bulk carrier concentration of a-ITZO was not affected by the heterostructure with Bi2Se3. In the case of the Bi2Se3 heterostructure, the carrier mobility and conductivity of a-ITZO were increased by 263.6% and 281.4%, respectively, whereas the resistivity of a-ITZO was reduced by 73.57%. This indicates that Bi2Se3 significantly improves the electrical properties of a-ITZO through its heterostructure, expanding its potential applications in electronic and thermoelectric devices.

Zinc oxide nanostructures enhanced photoluminescence by carbon-black nanoparticles in Moiré heterostructures.

ZnO/carbon-black heterostructures were synthesized using a sol-gel method and crystallized by annealing at 500 °C under 2 × 10-2 Torr for 10 min. The crystal structures and binding vibration modes were determined by XRD, HRTEM, and Raman spectrometry. Their surface morphologies were observed by FESEM. The Moiré pattern that is observed in the HRTEM images confirms that the carbon-black nanoparticles were covered by the ZnO crystals. Measurements of optical absorptance revealed that the optical band gap of the ZnO/carbon-black heterostructures increased from 2.33 to 2.98 eV as the carbon-black nanoparticle content increases from 0 to 8.33 × 10-3 mol owing to the Burstein-Moss effect. The photoluminescence intensities at the near-band edge and of the violet, and blue light were increased by factors about 68.3, 62.8, and 56.8, respectively, when the carbon-black contents is of the 2.03 × 10-3 mol. This work reveals that the proper carbon-black nanoparticle content involved increases the PL intensities of the ZnO crystals in the short wavelength regime, supporting their potential application in the light-emitting devices.

Effect of geographic isolation on genetic variation and population structure of Euphrasia nankotaizanensis, a threatened endemic alpine herb in Taiwan.

Euphrasia nankotaizanensis (Orobanchaceae) is a rare alpine herb that is endemic to Taiwan. Only four small populations remain in Xue, Nanhu, and Cilai Mountains of Taiwan. The distribution of alpine herbs is severely threatened by climate change, which influences genetic variation and population structure. In this study, we investigated the effects of the natural isolation of alpine habitats on the genetic diversity and geographic structure of populations of E. nankotaizanensis using chloroplast (cp) and nuclear DNA (nrDNA) markers. We found lower levels of genetic diversity in E. nankotaizanensis than in other alpine plants and little to no genetic variation within populations, which could be mainly attributed to the small population size and genetic drift. Only one nrDNA haplotype was present in each population. The lack of monophyly of the four populations in cpDNA probably resulted from lineage sorting or occasional long-distance seed dispersal. Phylogeographic analysis suggested that Nanhu Mountain was probably a refugium over the glacial maxima, agreeing with the potential refugia in central Taiwan. The STRUCTURE and AMOVA analyses revealed significant genetic differentiation in nrDNA among the mountains, which resulted from geographical isolation among these mountains. Estimates of the effective population size (Ne) and demography reflected lower Ne values and a recent population decline, probably implying a greater extinction risk for E. nankotaizanensis. We observed genetic depletion and considerable genetic differentiation among mountain populations, which should be considered in future conservation efforts for this species. In addition, this study provides important insights into the long-term potential of alpine herbs in Taiwan, which are useful for a better prediction of their responses to future climate change.

Metastatic tumor antigen 1 contributes to hepatocarcinogenesis posttranscriptionally through RNA-binding function.

BACKGROUND AND AIMS: Both nuclear and cytoplasmic overexpression of metastatic tumor antigen 1 (MTA1) contributes to tumorigenesis of HCC. Most studies have focused on nuclear MTA1 whose function is mainly a chromatin modifier regulating the expression of various cancer-promoting genes. By contrast, the molecular mechanisms of cytoplasmic MTA1 in carcinogenesis remain elusive. Here, we reveal a role of MTA1 in posttranscriptional gene regulation. APPROACH AND RESULTS: We conducted the in vitro and in vivo RNA-protein interaction assays indicating that MTA1 could bind directly to the 3'-untranslated region of MYC RNA. Mutation at the first glycine of the conserved GXXG loop within a K-homology II domain-like structure in MTA1 (G78D) resulted in the loss of RNA-binding activity. We used gain- and loss-of-function strategy showing that MTA1, but not the G78D mutant, extended the half-life of MYC and protected it from the lethal -7-mediated degradation. The G78D mutant exhibited lower activity in promoting tumorigenesis than wild-type in vitro and in vivo. Furthermore, RNA-immunoprecipitation sequencing analysis demonstrated that MTA1 binds various oncogenesis-related mRNAs besides MYC . The clinical relevance of cytoplasmic MTA1 and its interaction with MYC were investigated using HBV-HCC cohorts with or without early recurrence. The results showed that higher cytoplasmic MTA1 level and MTA1- MYC interaction were associated with early recurrence. CONCLUSIONS: MTA1 is a generic RNA-binding protein. Cytoplasmic MTA1 and its binding to MYC is associated with early recurrence in patients with HBV-HCC. This function enables it to regulate gene expression posttranscriptionally and contributes to hepatocarcinogenesis.

Fabrication, characterization and optical properties of Au-decorated Bi2Se3 nanoplatelets.

Au-decorated Bi2Se3 nanoplatelet heterostructures are fabricated by a two-step process of thermal CVD at 600 °C and magnetron sputtering at room-temperature. The crystal structures and binding energies of rhombohedral Bi2Se3 and FCC Au are determined by XRD, HRTEM, XPS, and Raman spectroscopy. XPS and Raman spectroscopy reveal the interaction between Au and Bi2Se3 by shifting in the binding energies of Au-Au, Au-Se and Bi-Se bonds and the wavenumber of A1g2 and Eg2 modes. Au-decorated Bi2Se3 nanoplatelet heterostructures are observed using FESEM, and confirmed by XPS, Raman spectroscopy, and HRTEM imaging. Their optical band gap of the Au-decorated Bi2Se3 nanoplatelet heterostructures increases with Au thickness about 1.92-fold as much as that of pristine Bi2Se3 (0.39 eV), owing to the Burstein-Moss effect. The optical absorptance of the Au-decorated Bi2Se3 nanoplatelet heterostructures revealed increment with wavelength from 200 to 500 nm and decrement with increasing wavelength from 500 to 800 nm.

Protective effects of corni fructus extract in mice with potassium oxonate-induced hyperuricemia.

Corni fructus is consumed as food and herbal medicine in Chinese culture. Studies have revealed that corni fructus exhibits potent antioxidant activity; however, few studies have investigated the ability of corni fructus to lower uric acid concentrations. In this study, the xanthine oxidase (XO) inhibition and uric acid-lowering effect of corni fructus extract (CFE) were evaluated in mice with potassium oxonate-induced hyperuricemia. Hyperuricemia is a chronic disease prevalent worldwide and is associated with high recurrence rates. In addition, drugs used to treat hyperuricemia induce side effects that discourage patient compliance. Hyperuricemia induces metabolic imbalances resulting in accumulative uric acid deposition in the joints and soft tissues. Hyperuricemia not only induces gout but also interrupts hepatic and renal function, thereby trigging severe inflammation and various complications, including obesity, nonalcoholic fatty liver disease, diabetes, and metabolic diseases. In this study, the ethyl acetate fraction (EAF) of CFE resulted in yields of antioxidant photochemical components significantly higher than those of CFEs formed using other substances. The EAF of CFE exhibited high free radical scavenging activity and XO inhibition and effectively lowered uric acid concentrations in the animal model of chemically induced hyperuricemia. The results of this study can serve as a reference for the prevention of preclinical gout as well as for functional food research.

Complete mitogenome of Antheraea formosana Sonan, 1937 (Lepidoptera: Saturniidae): an endemic silkmoth in Taiwan.

The complete mitogenome of an endemic silkmoth in Taiwan, Antheraea formosana, was determined using Illumina next-generation sequencing. The mitogenome is 15,318 bp in length and consists of 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region. The overall base composition of the mitogenome showed a high A + T bias, and the A + T content (80.2%) was significantly higher than the G + C content (19.8%). All PCGs use the typical ATN as the initiation codon, with the exception of cox2, which begins with GTG, respectively. The complete mitogenome was used to reconstruct a phylogenetic tree, indicating that A. formosana is more closely related to Antheraea assamensis than other Antheraea species, with 93.19% nucleotide similarity.

Enhanced Photocurrent of the Ag Interfaced Topological Insulator Bi2Se3 under UV- and Visible-Light Radiations.

Bi2Se3 is a topological quantum material that is used in photodetectors, owing to its narrow bandgap, conductive surface, and insulating bulk. In this work, Ag@Bi2Se3 nanoplatelets were synthesized on Al2O3(100) substrates in a two-step process of thermal evaporation and magnetron sputtering. X-ray diffractometer (XRD), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, and x-ray photoelectron spectroscopy (XPS) revealed that all samples had the typical rhombohedral Bi2Se3. Field-emission scanning electron microscopy (FESEM)-energy dispersive x-ray spectroscopy (EDS), XPS, and HRTEM confirmed the presence of the precipitated Ag. The optical absorptance of Bi2Se3 nanoplatelets in UV-visible range decreased with the Ag contents. Results of photocurrent measurements under zero-bias conditions revealed that the deposited Ag affected photosensitivity. A total of 7.1 at.% Ag was associated with approximately 4.25 and 4.57 times higher photocurrents under UV and visible light, respectively, than 0 at.% Ag. The photocurrent in Bi2Se3 at 7.1 at.% Ag under visible light was 1.72-folds of that under UV light. This enhanced photocurrent is attributable to the narrow bandgap (~0.35 eV) of Bi2Se3 nanoplatelets, the Schottky field at the interface between Ag and Bi2Se3, the surface plasmon resonance that is caused by Ag, and the highly conductive surface that is formed from Ag and Bi2Se3. This work suggests that the appropriate Ag deposition enhances the photocurrent in, and increases the photosensitivity of, Bi2Se3 nanoplatelets under UV and visible light.

Re-appraisal of Nertera (Rubiaceae) in Taiwan.

A revision of Nertera (Rubiaceae) in Taiwan was carried out by classical taxonomic methods and the presence of two endemic species was confirmed. Only one species, misapplied as N.granadensis, had been reported in the second edition of "Flora of Taiwan", but there were two additional endemic species in this genus: N.nigricarpa and N.taiwaniana confirmed. Nerteranigricarpa is characterised by the entire leaf, purple-black petals, black fruits and dark-purple seeds with raised striate. Nerterataiwaniana has leaves with undulated margins, yellowish-green petals, red fruits and yellow-white seeds without striate. N.granadensis is excluded from the flora of this Island.

Photosensing and Characterizing of the Pristine and In-, Sn-Doped Bi2Se3 Nanoplatelets Fabricated by Thermal V-S Process.

Pristine, and In-, Sn-, and (In, Sn)-doped Bi2Se3 nanoplatelets synthesized on Al2O3(100) substrate by a vapor-solid mechanism in thermal CVD process via at 600 °C under 2 × 10-2 Torr. XRD and HRTEM reveal that In or Sn dopants had no effect on the crystal structure of the synthesized rhombohedral-Bi2Se3. FPA-FTIR reveals that the optical bandgap of doped Bi2Se3 was 26.3%, 34.1%, and 43.7% lower than pristine Bi2Se3. XRD, FESEM-EDS, Raman spectroscopy, and XPS confirm defects (In3+Bi3+), (In3+V0), (Sn4+Bi3+), (V0Bi3+), and (Sn2+Bi3+). Photocurrent that was generated in (In,Sn)-doped Bi2Se3 under UV(8 W) and red (5 W) light revealed stable photocurrents of 5.20 × 10-10 and 0.35 × 10-10 A and high Iphoto/Idark ratios of 30.7 and 52.2. The rise and fall times of the photocurrent under UV light were 4.1 × 10-2 and 6.6 × 10-2 s. Under UV light, (In,Sn)-dopedBi2Se3 had 15.3% longer photocurrent decay time and 22.6% shorter rise time than pristine Bi2Se3, indicating that (In,Sn)-doped Bi2Se3 exhibited good surface conduction and greater photosensitivity. These results suggest that In, Sn, or both dopants enhance photodetection of pristine Bi2Se3 under UV and red light. The findings also suggest that type of defect is a more important factor than optical bandgap in determining photo-detection sensitivity. (In,Sn)-doped Bi2Se3 has greater potential than undoped Bi2Se3 for use in UV and red-light photodetectors.

Structure and Photoluminescence Properties of Thermally Synthesized V2O5 and Al-Doped V2O5 Nanostructures.

Al-free and Al-doped V2O5 nanostructures were synthesized by a thermal-chemical vapor deposition (CVD) process on Si(100) at 850 °C under 1.2 × 10-1 Torr via a vapor-solid (V-S) mechanism. X-ray diffraction (XRD), Raman, and high-resolution transmission electron microscopy (HRTEM) confirmed a typical orthorhombic V2O5 with the growth direction along [110]-direction of both nanostructures. Metallic Al, rather than Al3+-ion, was detected by X-ray photoelectron spectroscopy (XPS), affected the V2O5 crystallinity. The photoluminescence intensity of V2O5 nanostructure at 1.77 and 1.94 eV decreased with the increasing Al-dopant by about 61.6% and 59.9%, attributing to the metallic Al intercalated between the V2O5-layers and/or filled in the oxygen vacancies, which behaved as electron sinks. Thus the Al-doped V2O5 nanostructure shows the potential applications in smart windows and the electrodic material in a Li-ion battery.

Permanent Inactivation of HBV Genomes by CRISPR/Cas9-Mediated Non-cleavage Base Editing.

Current antiviral therapy fails to cure chronic hepatitis B virus (HBV) infection because of persistent covalently closed circular DNA (cccDNA). CRISPR/Cas9-mediated specific cleavage of cccDNA is a potentially curative strategy for chronic hepatitis B (CHB). However, the CRISPR/Cas system inevitably targets integrated HBV DNA and induces double-strand breaks (DSBs) of host genome, bearing the risk of genomic rearrangement and damage. Herein, we examined the utility of recently developed CRISPR/Cas-mediated "base editors" (BEs) in inactivating HBV gene expression without cleavage of DNA. Candidate target sites of the SpCas9-derived BE and its variants in HBV genomes were screened for generating nonsense mutations of viral genes with individual guide RNAs (gRNAs). SpCas9-BE with certain gRNAs effectively base-edited polymerase and surface genes and reduced HBV gene expression in cells harboring integrated HBV genomes, but induced very few insertions or deletions (indels). Interestingly, some point mutations introduced by base editing resulted in simultaneous suppression of both polymerase and surface genes. Finally, the episomal cccDNA was successfully edited by SpCas9-BE for suppression of viral gene expression in an in vitro HBV infection system. In conclusion, Cas9-mediated base editing is a potential strategy to cure CHB by permanent inactivation of integrated HBV DNA and cccDNA without DSBs of the host genome.

Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Overexpression of metastatic tumor antigen 1 (MTA1) was correlated with poor prognosis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC). The aim of this study was to examine the clinical significance of the expression of MTA1 and its exon 4-excluded form (MTA1dE4), the most abundant spliced variant of MTA1, in patients receiving curative resection for HBV-HCC. We collected 102 patients with HBV-HCC and received curative resection retrospectively and examined the expressions level of total MTA1/MTA1dE4 in their paired nontumor and tumor liver tissues by using RT-qPCR. The association between MTA1/MTA1dE4 expression and various tumor features as well as tumor recurrence was analyzed. During the median follow-up period of 4 years, 25 patients (24.5%) showed early recurrence (within 12 months postresection) and 42 (54.5%) showed late recurrence. In Kaplan-Meier analysis, MTA1dE4 overexpression in tumor, but not MTA1, was associated with early recurrence (P = 0.0365), but not late recurrence. In multivariate analysis, only alpha-fetoprotein (AFP) ≥200 ng/mL (P = 0.006) and large tumor size (P = 0.027) were correlated with early recurrence. In the subgroup of patients with AFP <200 ng/mL, high MTA1dE4, but not total MTA1, expression could help predict early recurrence (P = 0.0195). In vitro, wound healing and invasion assays were performed in HCC cells, and MTA1dE4 was found to exhibit a higher ability in promoting migration and invasion of hepatoma cells than full-length MTA1. Conclusion: MTA1dE4 expression is correlated with more aggressive tumor characteristics and might serve as a more sensitive marker for early recurrence of HBV-HCC, especially for low-AFP patients.

Entropy-Based Clustering Algorithm for Fingerprint Singular Point Detection.

Fingerprints have long been used in automated fingerprint identification or verification systems. Singular points (SPs), namely the core and delta point, are the basic features widely used for fingerprint registration, orientation field estimation, and fingerprint classification. In this study, we propose an adaptive method to detect SPs in a fingerprint image. The algorithm consists of three stages. First, an innovative enhancement method based on singular value decomposition is applied to remove the background of the fingerprint image. Second, a blurring detection and boundary segmentation algorithm based on the innovative image enhancement is proposed to detect the region of impression. Finally, an adaptive method based on wavelet extrema and the Henry system for core point detection is proposed. Experiments conducted using the FVC2002 DB1 and DB2 databases prove that our method can detect SPs reliably.

Eicosapentaenoic acid reduces indoleamine 2,3-dioxygenase 1 expression in tumor cells.

Marine plants and animals have omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is required for biological processes, but humans are unable to synthesize them and must be obtained from dietary sources. EPA has been used as an antitumor agent but the molecular mechanisms for the regulation of tumor microenvironment immunity by EPA are still unknown. The indoleamine 2,3-dioxygenase 1 (IDO) catalyzes conversion of tryptophan to kynurenine to induce immune evasion in tumor microenvironment. In this study, EPA inhibited the expression of IDO via downregulation of protein kinase B (Akt)/mammalian targets of rapamycin (mTOR) signaling pathway in tumor cells. Meanwhile, a significant decrease in kynurenine levels and increase in T cell survival were observed after tumor cells treated with EPA. The results demonstrated that EPA can activate host antitumor immunity by inhibiting tumor IDO expression. Therefore, our finding suggests that EPA can be enormous potential for cancer immunotherapy.

Protective effect of N-acetylcysteine on progression to end-stage renal disease: Necessity for prospective clinical trial.

BACKGROUND: We aimed to evaluate the potential benefits of N-acetylcysteine (NAC) on the risk of chronic kidney disease (CKD) progression to dialysis-requiring end-stage renal disease (ESRDd). METHODS: In a population-based cohort study of 145,062 individuals, 123,608 CKD patients who were followed up for 10years were included, and CKD patients treated with NAC (ICD-9-CM) were compared with those who were not treated. Using propensity score matching, we analyzed the predictors of CKD progression to ESRDd by Cox proportional hazards regression with adjustments for sex, age, and comorbidities, and evaluated the effect of NAC using cumulative defined daily dose (cDDD). RESULTS: NAC use was associated with a reduced risk for progression to ESRDd [hazard ratio (HR), 0.819; 95% confidence interval (CI), 0.781-0.965; P=0.017]. Risk reduction was proportional to cDDD in NAC users compared with that in NAC non users (HR, 0.835, 0.811, and 0.799 for cDDD 91-180, 181-360, and >360, respectively; P for trend=0.018). Risk reduction was apparent in women (P=0.001) and in younger-aged patients of 18-29years (P=0.021) and 30-39years (P=0.033), in the presence of hypertension (P=0.003), and in the absence of diabetes mellitus (P=0.042) and congestive heart failure (P=0.036). CONCLUSION: NAC use was associated with a reduced risk for progression to ESRDd. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway.

Death-associated protein kinase (DAPK) has been found to be induced by IFN, but its antiviral activity remains elusive. Therefore, we investigated whether DAPK plays a role in the pegylated IFN-α (peg-IFN-α)-induced antiviral activity against hepatitis C virus (HCV) replication. Primary human hepatocytes, Huh-7, and infectious HCV cell culture were used to study the relationship between peg-IFN-α and the DAPK-mammalian target of rapamycin (mTOR) pathways. The activation of DAPK and signaling pathways were determined using immunoblotting. By silencing DAPK and mTOR, we further assessed the role of DAPK and mTOR in the peg-IFN-α-induced suppression of HCV replication. Peg-IFN-α up-regulated the expression of DAPK and mTOR, which was associated with the suppression of HCV replication. Overexpression of DAPK enhanced mTOR expression and then inhibited HCV replication. In addition, knockdown of DAPK reduced the expression of mTOR in peg-IFN-α-treated cells, whereas silencing of mTOR had no effect on DAPK expression, suggesting mTOR may be a downstream effector of DAPK. More importantly, knockdown of DAPK or mTOR significantly mitigated the inhibitory effects of peg-IFN-α on HCV replication. In conclusion, our data suggest that the DAPK-mTOR pathway is critical for anti-HCV effects of peg-IFN-α.