Gold nanostructures/quantum dots for the enhanced efficiency of organic solar cells.

Incorporating gold nanoparticles (AuNPs) into organic solar cell (OSC) structures provides an effective means to manipulate light-matter interactions. AuNPs have been used as plasmonic-enhancement and light-trapping materials in OSCs and exhibit diverse single and mixed morphologies. Substantial near-field enhancement from metal periodic structures has consistently demonstrated high enhancement in solar cell efficiency. Additionally, coupling with atomic gold clusters in the form of gold quantum dots holds promise for light harvesting through fluorescence phenomena. The configured devices optimize light utilization in OSCs by considering factors such as the morphology, position, and hybridization of localized surface plasmon resonance, propagating surface plasmon resonance, and fluorescence phenomena. This optimization enhances light absorption, scattering, and efficient trapping facilitated by gold nanostructures/quantum dots. The configured setup exhibits multiple effects, concurrently improving plasmonic and fluorescence responses under solar irradiation, thereby enhancing energy conversion performance. Integrating plasmonic nanostructures with OSCs can address fundamental issues, providing opportunities to enhance the light-absorption intensity and charge transfer efficiency at intra and intermolecular levels. This comprehensive review demonstrates that the greatest improvement in solar cell efficiency exceeded 30% compared with the reference cells.

ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis.

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

AIM: An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. METHODS: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1 log IU/mL from baseline) were evaluated. RESULTS: The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was -1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. CONCLUSIONS: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Hepatocellular organellar abnormalities following elimination of hepatitis C virus.

BACKGROUND AND AIMS: The future development of hepatocellular carcinoma (HCC) in patients after sustained virologic response (SVR) is an important issue. The purposes of this study were to investigate pathological alterations in organelle of the liver of SVR patients and to characterize organelle abnormalities that may be related to carcinogenesis after SVR. METHODS: The ultrastructure of liver biopsy specimens from patients with chronic hepatitis C (CHC) and SVR were compared to cell and mouse models and assessed semi-quantitatively using transmission electron microscopy. RESULTS: Hepatocytes in patients with CHC showed abnormalities in the nucleus, mitochondria, endoplasmic reticulum, lipid droplet, and pericellular fibrosis, comparable to those seen in hepatitis C virus (HCV)-infected mice and cells. DAA treatment significantly reduced organelle abnormalities such as the nucleus, mitochondria, and lipid droplet in the hepatocytes of patients and mice after SVR, and cured cells, but it did not change dilated/degranulated endoplasmic reticulum and pericellular fibrosis in patients and mice after SVR. Further, samples from patients with a post-SVR period of >1 year had significantly larger numbers of abnormalities in the mitochondria and endoplasmic reticulum than those of <1 year. A possible cause of organelle abnormalities in patients after SVR could be oxidative stress of the endoplasmic reticulum and mitochondria associated with abnormalities of the vascular system due to fibrosis. Interestingly, abnormal endoplasmic reticulum was associated with patients with HCC for >1 year after SVR. CONCLUSIONS: These results indicate that patients with SVR exhibit a persistent disease state and require long-term follow-up to detect early signs of carcinogenesis.

Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study.

BACKGROUND: Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations. RESULTS: A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score. CONCLUSIONS: This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.

Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

Tunable surface plasmon resonance enhanced fluorescence via the stretching of a gold quantum dot-coated aluminum-coated elastomeric grating substrate.

In this study, the surface plasmon resonance (SPR)-enhanced fluorescence properties of gold quantum dots (AuQDs) on an aluminum (Al)-coated polydimethylsiloxane (PDMS) grating substrate were investigated by changing the grating pitch via mechanical stretching. The SPR-excitation wavelength of the AuQDs/Al-coated PDMS-grating substrate was tuned by changing the incident light angle from 5° to 60° and stretching it from 0 to 1.0 mm. In addition, the SPR-enhanced fluorescence tuning ability was studied using an AuQD/Al-coated PDMS-grating film by stretching the substrate. The SPR-enhanced fluorescence (SPF) of the AuQDs on the Al-grating was observed using a violet laser as the excitation source at 405 nm with p-polarization. The wavelengths of the SPR excitation, corresponding to the SP-dispersion mode of +1, were shifted to a longer wavelength upon stretching the grating substrate from 0 to 1.0 mm. By stretching the AuQDs/Al-grating PDMS substrate, the SPR-enhanced fluorescence intensity increased at fixed incident angles of 15° and 35°, whereas the SPR-enhanced fluorescence intensity decreased at 40°. Moreover, the SPF could be tuned to exhibit different properties in tunable optical sensors.

Plasmonic photothermal properties of silver nanoparticle grating films.

The plasmon-induced photothermal effect offers effective light-to-heat conversion systems. In this study, we fabricate plasmonic photothermal silver nanoparticle (AgNP) grating films to produce highly effective plasmon-induced heat generation films. AgNP films provide effective heat generation by localized surface plasmon excitation in the void of the AgNP films. The heat generated at a AgNP film by irradiation of solar light is 3.4 times higher than that generated at the reference flat evaporated-Ag film. Furthermore, simultaneous excitation of localized surface plasmons and propagating surface plasmons is confirmed to be obtained on AgNP grating films by finite-difference time-domain simulation and reflectivity measurements. The AgNP grating film is created by the nanoimprinting technique. The grating structure on AgNPs further enhances electric field intensity in the large area of the film, which results in higher heat generation. Thus, 5.4 times higher heat generation is achieved compared with that of the reference flat evaporated-Ag film.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C.

Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.

Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

The effect of gold quantum dots/grating-coupled surface plasmons in inverted organic solar cells.

We studied the effect of gold quantum dots (AuQDs)/grating-coupled surface plasmon resonance (GC-SPR) in inverted organic solar cells (OSCs). AuQDs are located within a GC-SPR evanescent field in inverted OSCs, indicating an interaction between GC-SPR and AuQDs' quantum effects, subsequently giving rise to improvement in the performance of inverted OSCs. The fabricated solar cell device comprises an ITO/TiO2/P3HT : PCBM/PEDOT : PSS : AuQD/silver grating structure. The AuQDs were loaded into a hole transport layer (PEDOT : PSS) of the inverted OSCs to increase absorption in the near-ultraviolet (UV) light region and to emit visible light into the neighbouring photoactive layer, thereby achieving light-harvesting improvement of the device. The grating structures were fabricated on P3HT:PCBM layers using a nanoimprinting technique to induce GC-SPR within the inverted OSCs. The AuQDs incorporated within the strongly enhanced GC-SPR evanescent electric field on metallic nanostructures in the inverted OSCs improved the short-circuit current and the efficiency of photovoltaic devices. In comparison with the reference OSC and OSCs with only green AuQDs or only metallic grating, the developed device indicates enhancement of up to 16% power conversion efficiency. This indicates that our light management approach allows for greater light utilization of the OSCs because of the synergistic effect of G-AuQDs and GC-SPR.

Dual-mode surface plasmon resonance sensor chip using a grating 3D-printed prism.

The method for fabricating a grating prism surface plasmon resonance (SPR) sensor chip was developed. The grating prism was 3D-printed by a stereolithography 3D printer and subsequently created a grating pattern by soft lithography. A gold film was thermally evaporated on the grating prism. Moreover, a liquid cell was 3D-printed and assembled into a gold-coated grating prism. To make the sensor chip compact and practical, a compatible prism holder was 3D-printed by a fused deposition model 3D printer. The SPR sensor chip was mounted on the rotation stage and the SPR spectrum was recorded by spectrometer. The SPR excitation of the sensor chip can be extended to the near-infrared region by creating a grating pattern on the prism surface. A gold-coated grating prism exhibited dual modes of SPR excitations, namely, prism-coupling SPR (PC-SPR) and grating-coupling SPR (GC-SPR). The dual-mode SPR excitation was observed at the incident angles of 45°-80°. When the incident angle increased, the SPR excitation of the PC-SPR mode exhibited a blue shift in the wavelength region of 480-690 nm, whereas the GC-SPR mode exhibited a red shift in the wavelength region of 670-770 nm. The surface plasmon (SP) dispersion obtained from the dual-mode SPR configuration confirmed observable PC-SPR (which corresponded to + SP0 of the gold-resin interface) and GC-SPR (which corresponded to -SP+1 of the gold-air interface), which could be excited from the developed substrate. The refractive index sensitivities of the PC-SPR and GC-SPR modes were 2924.4 and 414.9 nm RIU-1, respectively. The SPR excitations of the sensor chip exhibited a simultaneous shift when the local refractive index of the materials adjacent to the gold-coated grating prism surface was changed, especially the material that had overlapping light absorption at the SPR excitation wavelength. Using this fabrication process, the prism is designed and then printed; moreover, the grating pattern on the prism surface can be employed to tune the SPR excitation wavelength of the sensor chip for the versatility and broad perspective of the optical sensing-based SPR.

Sequential therapy from entecavir to tenofovir alafenamide versus continuous entecavir monotherapy for patients with chronic hepatitis B.

BACKGROUND AND AIM: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. METHODS: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. RESULTS: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. CONCLUSIONS: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV.

Colorimetric Detection Based on Localized Surface Plasmon Resonance for Determination of Chemicals in Urine.

Colorimetric sensors based on localized surface plasmon resonance (LSPR) have attracted much attention for biosensor and chemical sensor applications. The unique optical effect of LSPR is based on the nanostructure of noble metals (e.g., Au, Ag, and Al) and the refractive index of the environment surrounding these metal nanomaterials. When either the structure or the environment of these nanomaterials is changed, their optical properties change and can be observed by spectroscopic techniques or the naked eye. Colorimetric-probe-based LSPR provides a simple, rapid, real-time, nonlabelled, sensitive biochemical detection and can be used for point-of-care testing as well as rapid screening for the diagnosis of various diseases. Gold and silver nanoparticles, which are the two most widely used plasmonic nanomaterials, demonstrate strong and sensitive LSPR signals that can be used for the selective detection of several chemicals in biochemical compounds provided by the human body (e.g., urine and blood). This information can be used for the diagnosis of several human health conditions. This paper provides information regarding colorimetric probes based on LSPR for the detection of three major chemicals in human urine: creatinine, albumin, and glucose. In addition, the mechanisms of selective detection and quantitative analysis of these chemicals using metal nanoparticles are discussed along with colorimetric-detection-based LSPR for many other specific chemicals that can be detected in urine, such as catecholamine neurotransmitters, thymine, and various medicines. Furthermore, issues regarding the use of portable platforms for health monitoring with colorimetric detection based on LSPR are discussed.

Colorimetric Determination of Urinary Creatinine in Proteinuria Patients by Chromaticity Analysis of Gold Nanoparticle Colloidal Solutions.

Several scientific works have reported the use of colloidal gold nanoparticle (AuNP) solutions as a colorimetric probe for creatinine detection. Nonetheless, urinary protein is one of the primary chemical components that can interfere with creatinine detection. In this work, we developed a colorimetric probe using AuNP colloidal solution to detect creatinine in the urine of proteinuria patients. A microchamber array was prepared to minimize the sample volume and was used to simultaneously perform spectral recording and image acquisition of several samples. The analyzed volume for each sample was 15 µL. A camera coupled with liquid crystal tunable filters was used to record hyperspectral images, and the signals were then converted to localized surface plasmon resonance (LSPR) spectra. Color changes in the AuNP colloidal solution in the presence of varying concentrations of creatinine and human serum albumin (HSA) indicated different features and could be detected by a hyperspectral imaging technique. The relevant concentration ranges of creatinine and HSA were 5 - 200 and 50 - 250 mg dL-1, respectively. Furthermore, a smartphone camera was adopted to record a color mapping image of the AuNP colloidal solution in the presence of creatinine and HSA at these concentration ranges. Contour plots of red and blue chromaticity levels from color mappings were produced, and 2D fitting equations obtained from these contour plots were adopted to determine the creatinine concentration in the urine of proteinuria patients. This practical technique can be used for screening and can be further developed as a household biosensing device for urinalysis.

Specific Deletion of p16INK4a with Retention of p19ARF Enhances the Development of Invasive Oral Squamous Cell Carcinoma.

The cyclin-dependent kinase inhibitor 2A (CDKN2A)/alternate reading frame (ARF) locus consists of two overlapping tumor suppressor genes, p16INK4a and p14ARF (p19ARF in mice), encoding two unrelated proteins in alternative reading frames. Previous reports suggest that p16INK4a and p14ARF alterations independently exhibit differential roles, and p16INK4a is more closely associated with a poor prognosis in oral cancer. However, the role of p16INK4a-specific loss in oral squamous cell carcinogenesis remains unclear. The authors assessed chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced multistep oral squamous cell carcinogenesis in mice carrying p16INK4a-specific loss with retention of the p19ARF gene (p16INK4a-/-). 4NQO-treated p16-/- mice exhibited a higher incidence and multiplicity of oral squamous cell carcinoma (OSCC) development relative to 4NQO-treated wild-type mice. 4NQO-treated p16INK4a-/- OSCC cells exhibited higher proliferation and up-regulation of Arf, transcription factor E2f1, tumor protein p63 (tp63), and oncogenic ΔNp63, an isoform p63, compared with observations in 4NQO-treated wild-type OSCC cells. Furthermore, the overexpression of oncogenic ΔNp63 was associated with human OSCC. In conclusion, these results in mice indicate the biological significance of p16INK4a-specific loss with retention of p19ARF in oral squamous cell carcinogenesis, and ΔNp63 may be a potential target for OSCC.

Enhancement of organic solar cell performance by incorporating gold quantum dots (AuQDs) on a plasmonic grating.

The incorporation of metallic nanoobjects into devices allows to increase light harvesting, which increases the device performance. In this study, we used a combination of gold quantum dots and grating-coupled surface plasmon resonance (GCSPR) to improve the performance of organic solar cells (OSCs) with a poly(3-hexylthiophene-2,5-diyl) (P3HT):[6,6]-phenyl C61 butyric acid methyl ester (PCBM) photoactive layer. Gold quantum dots with a green fluorescent color (green-AuQD) were loaded into a hole transport layer (HTL) aiming to harvest photons in the UV region and emit visible light into the neighboring photoactive layer. Meanwhile, plasmonic grating structures, which were created on the photoactive layer surfaces via the nanoimprinting technique, provided an enhancement effect through light scattering and GCSPR. Thus, an excellent enhancement of OSC efficiency with a significant increase in short circuit photocurrent (J SC) and power conversion efficiency (PCE) in comparison to that of the reference cell was achieved. The fabricated device provides a J SC value as high as 8.41 mA cm-2 (a 14.11% enhancement) and a PCE value of 3.91% (a 19.57% enhancement). The systematic study clearly reveals that the remarkable enhancement of OSC efficiency is achieved by incorporating both AuQD and plasmonic grating.

Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema.

BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.

Single nucleotide polymorphisms associated with elevated alanine aminotransferase in patients receiving asunaprevir plus daclatasvir combination therapy for chronic hepatitis C.

AIMS: Drug-induced liver damage characterized by serum alanine aminotransferase (ALT) elevation often occurs in direct-acting antiviral (DAA) combination therapy for chronic hepatitis C virus (HCV) infection. This study explored single nucleotide polymorphisms (SNPs) at drug metabolism- or transport-related genes that were associated with ALT elevation in asunaprevir plus daclatasvir therapy. METHODS: Subjects were 185 Japanese patients with chronic HCV genotype 1b infection who received asunaprevir plus daclatasvir therapy. Tag SNPs at possible metabolizing enzyme and transporter genes, which were involved in the pharmacokinetics of asunaprevir and daclatasvir, were selected. RESULTS: Among the tag SNPs analyzed, CYP3A4 rs4646437 was significantly associated with ALT elevation (p = 0.013): maximum ALT values in patients with genotype CC were higher than those in patients with genotype non-CC (allele T). The proportion of grades 2-4 in genotype CC patients were significantly greater than those in genotype non-CC patients (p = 0.028). No patients with genotype non-CC showed grade ≥2 ALT elevation. In multivariate analysis, rs4646437 genotype CC and cirrhosis were significant, independent factors associated with grade ≥1 ALT elevation (odds ratio, 2.83 and 1.88; p = 0.040 and 0.045, respectively). In exploratory analyses, although serum concentrations of asunaprevir and daclatasvir were not correlated with maximum ALT values or rs4646437 genotypes, asunaprevir concentrations in patients with grade ≥1 ALT elevation were significantly higher than those in patients with grade <1 ALT elevation (P = 0.023). CONCLUSIONS: CYP3A4 rs4646437 was found to be significantly and independently associated with ALT elevation in Japanese patients receiving ASV plus DCV therapy. Notably, none of the patients with rs4646437 genotype non-CC (allele T) had grade ≥2 ALT elevation. SNP genotyping prior to treatment might be useful for carefully monitoring patients to complete treatment safely.