Identification of environmental factors that promote intestinal inflammation.

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity2. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPß signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.

The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery.

Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface protein (LHBS) expression increased in the tumors, implicating that it played a significant role in tumor development. To detect the LHBS in serum and evaluate its association with HCC progression, we developed a sandwich ELISA method for LHBS. The mouse monoclonal antibodies for the pre-S1, pre-S2, and HBS regions were in-house generated and constructed into a chemiluminescent sandwich ELISA system, which allowed sensitive and quantitative measurement of the protein. Using this ELISA assay, we estimated the expression of LHBS in CHB and HCC patients. We found that the serum LHBS level was correlated with the HBS but not the viral titer in serum, indicating that HBV surface proteins' expression does not mainly depend on viral replication. Moreover, both serum LHBS and HBS levels were lower in the HCC patients than in the CHB. The liver LHBS signals, detected by immunohistochemical staining, showed significant correlations with the serum LHBS and HBS levels. In addition, the more elevated serum LHBS but not HBS level was significantly associated with cirrhosis and worse disease-free and overall survival rates, based on the multivariate analysis. Conclusion: LHBS plays a specific role in tumor progression and is an independent parameter associated with HCC recurrence. Serum LHBS represents a novel noninvasive biomarker for HCC patients with a worse prognosis after surgery.

Growth of GaN Thin Films Using Plasma Enhanced Atomic Layer Deposition: Effect of Ammonia-Containing Plasma Power on Residual Oxygen Capture.

In recent years, the application of (In, Al, Ga)N materials in photovoltaic devices has attracted much attention. Like InGaN, it is a direct band gap material with high absorption at the band edge, suitable for high efficiency photovoltaic devices. Nonetheless, it is important to deposit high-quality GaN material as a foundation. Plasma-enhanced atomic layer deposition (PEALD) combines the advantages of the ALD process with the use of plasma and is often used to deposit thin films with different needs. However, residual oxygen during growth has always been an unavoidable issue affecting the quality of the resulting film, especially in growing gallium nitride (GaN) films. In this study, the NH3-containing plasma was used to capture the oxygen absorbed on the growing surface to improve the quality of GaN films. By diagnosing the plasma, NH2, NH, and H radicals controlled by the plasma power has a strong influence not only on the oxygen content in growing GaN films but also on the growth rate, crystallinity, and surface roughness. The NH and NH2 radicals contribute to the growth of GaN films while the H radicals selectively dissociate Ga-OH bonds on the film surface and etch the grown films. At high plasma power, the GaN film with the lowest Ga-O bond ratio has a saturated growth rate, a better crystallinity, a rougher surface, and a lower bandgap. In addition, the deposition mechanism of GaN thin films prepared with a trimethylgallium metal source and NH3/Ar plasma PEALD involving oxygen participation or not is also discussed in the study.

Effect of Growth Temperature on the Characteristics of CsPbI3-Quantum Dots Doped Perovskite Film.

In this study, adding CsPbI3 quantum dots to organic perovskite methylamine lead triiodide (CH3NH3PbI3) to form a doped perovskite film filmed by different temperatures was found to effectively reduce the formation of unsaturated metal Pb. Doping a small amount of CsPbI3 quantum dots could enhance thermal stability and improve surface defects. The electron mobility of the doped film was 2.5 times higher than the pristine film. This was a major breakthrough for inorganic quantum dot doped organic perovskite thin films.

Investigation of the Stability of Methylammonium Lead Iodide (MAPbI3) Film Doped with Lead Cesium Triiodide (CsPbI3) Quantum Dots under an Oxygen Plasma Atmosphere.

In this study, we describe composited perovskite films based on the doping of lead cesium triiodide (CsPbI3) quantum dots (QDs) into methylammonium lead iodide (MAPbI3). CsPbI3 QDs and MAPbI3 were prepared by ligand-assisted re-precipitation and solution mixing, respectively. These films were optimized by oxygen plasma treatment, and the effect of powers from 0 to 80 W on the structural properties of the composited perovskite films is discussed. The experimental results showed that the light-harvesting ability of the films was enhanced at 20 W. The formation of the metastable state (lead(II) oxide and lead tetroxide) was demonstrated by peak differentiation-imitating. A low power enhanced the quality of the films due to the removal of organic impurities, whereas a high power caused surface damage in the films owing to the severe degradation of MAPbI3.

The Influence of Oxygen Plasma on Methylammonium Lead Iodide (MAPbI3) Film Doped with Lead Cesium Triiodide (CsPbI3).

In recent years, the study of organic-inorganic halide perovskite as an optoelectronics material has been a significant line of research, and the power conversion efficiency of solar cells based on these materials has reached 25.5%. However, defects on the surface of the film are still a problem to be solved, and oxygen plasma is one of the ways to passivate surface defects. In order to avoid destroying the methylammonium lead iodide (MAPbI3), the influence of plasma powers on film was investigated and the cesium triiodide (CsPbI3) quantum dots (QDs) were doped into the film. In addition, it was found that oxygen plasma can enhance the mobility and carrier concentration of the MAPbI3 film.

Requirement of cyclin-dependent kinase function for hepatitis B virus cccDNA synthesis as measured by digital PCR.

INTRODUCTION AND OBJECTIVES: HBV covalently closed circular (ccc) DNA is the key player in viral persistence and an important predictive biomarker for hepatitis relapse. Precise quantification of intracellular cccDNA is challenging because cccDNA is present in very low levels in hepatocytes, where it also co-exists with a large excess amount of relaxed circular (rc) DNA. We aimed to develop a highly sensitive cccDNA detection method for cccDNA quantification by digital PCR (dPCR). PATIENTS OR MATERIALS AND METHODS: A standard plasmid containing the whole HBV genome in the closed circular conformation was employed to characterize the performance of dPCR. rcDNA in the growth medium of HBV-producing HepAD38 cells was used as a matrix for cccDNA detection. Intrahepatic cccDNA measurement by dPCR and qPCR was performed to determine the correlation of the analysis results for the two methods. RESULTS: The limit of detection (LOD) of the cccDNA dPCR was 1.05copy/µl, and the linear range of detection was 1.02×104copies/µl, achieving a dynamic detection range of 104-fold. cccDNA measurement using excess rcDNA as the matrix did not reveal false-positive detection, indicating that dPCR was highly specific. In the HepAD38 cells, the cccDNA levels measured by dPCR were highly correlated with those measured by qPCR but had a higher sensitivity. The CDK inhibitor AZD-5438 was found to block intracellular cccDNA synthesis. CONCLUSIONS: Dpcr greatly improved the sensitivity and specificity of cccDNA detection. Host CDK activities are likely required for cccDNA synthesis. dPCR can potentially be applied for drug screening for effective cccDNA inhibitors.

NEK2 Promotes Hepatoma Metastasis and Serves as Biomarker for High Recurrence Risk after Hepatic Resection.

INTRODUCTION AND AIM: Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients. MATERIAL AND METHODS: The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence. RESULTS: NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2 level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. CONCLUSIONS: NEK2 plays a significant role in cell cycle progression in the inter- and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.

Effects of green tea extract on overweight and obese women with high levels of low density-lipoprotein-cholesterol (LDL-C): a randomised, double-blind, and cross-over placebo-controlled clinical trial.

BACKGROUND: This study aims to examine the effects of green tea extract (GTE) supplement on overweight and obese women with high levels of low density lipoprotein-cholesterol (LDL-C). METHODS: The randomized, double-blind, crossover and placebo-controlled clinical trial was conducted from August 2012 to December 2013. Seventy-three out of 90 subjects aged between 18 and 65 years, with body mass index (BMI) ≥ 27 kg/m2 and LDL-C ≥ 130 mg/dl were included in the analysis. The subjects were randomly divided into Groups A and B. Group A received GTE supplement treatment for the first 6 weeks, while Group B received placebo daily. After 6 weeks of treatment and 14 days of washout period, Group A switched to placebo and Group B switched to GTE treatment for 6 weeks. The reduction of LDL-C level between treatments was assessed as the outcome. Additionally, anthropometric measurements, plasma lipoproteins and hormone peptides of both groups were measure at the beginning of weeks 6, 8, and 14 after treatment. RESULTS: Subjects treated with GTE (n = 73) for 6 weeks showed significant differences, with 4.8% (p = 0.048) reduction in LDL-C and 25.7% (p = 0.046) increase in leptin. However, there was no statistical difference in the levels of total cholesterol, triglyceride and high density lipoprotein between the GTE and placebo groups after treatments. CONCLUSIONS: This study shows that green tea extract effectively increases leptin and reduces LDL in overweight and obese women after 6 weeks of treatment even though there were no significant changes in other biochemical markers related to overweight. TRIAL REGISTRATION: This clinical trial is registered with ClinicalTrials.gov: NCT02116517 on 17 April 2014. Retrospectively registered. The first patient enrolled in October 2012 and the study was completed December 2013.

Analysis of SmartPlug Insertion-Related Complications.

PURPOSE: To evaluate the complications and the treatment results of SmartPlug-related complications. METHODS: Retrospective review of all patients from a single medical hospital who received SmartPlug (Medennium, Inc., Irvine, CA) insertions from October 2007 to February 2014. All patients who developed SmartPlug-related canaliculitis and pyogenic granuloma were analyzed. Lacrimal irrigation with antibiotics was performed in most patients. RESULTS: Six hundred thirty-one eyes received SmartPlug insertion and 18 eyes developed SmartPlug-related complications (14 canaliculitis and 4 pyogenic granuloma). The mean time interval from insertion to development of the complications is 3.0 (0.5-6.9) years. Sixteen eyes received lacrimal irrigation with antibiotics, and all the eyes showed improvement without recurrence. The other two eyes had recurrence of granuloma pyogenica only after surgical excision. CONCLUSIONS: SmartPlug-related complications, including canaliculitis and granuloma pyogenica, required long-term follow-up. Most of the complications can be cured by lacrimal irrigation of antibiotics.

Evaluation of the Upper Airway Morphology: The Role of Cone Beam Computed Tomography.

Cone beam computed tomography (CBCT) has several applications in dentomaxillofacial diagnosis. Frequently, the imaged volume encompasses the upper airway. This article provides a systematic approach to airway analysis and the implications of the anatomic and pathologic alterations. It discusses the role of CBCT in management of obstructive sleep apnea (OSA) patients. This paper also highlights technological advances that combine CBCT imaging with computational modeling of the airway and the potential clinical applications of such technologies.

The long-term trend in utilization of traditional Chinese medicine and associated factors among older people in Taiwan.

BACKGROUND: Both the size of the older population and the use of complementary and alternative medicine are increasing worldwide. This study evaluated the long-term trend in utilization of traditional Chinese medicine (TCM) and associated factors among older people in Taiwan. METHODS: Using the database of population-based interview surveys, we evaluated the one-month prevalence of TCM use among 13,945 older people aged over 65 years from 2001-2017. The sociodemographic status and medical comorbidities of older people who did and did not use TCM were compared by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multiple logistic regressions. RESULTS: The one-month prevalence of TCM use increased from 5.5% in 2001 to 9.1% in 2017 among older people in Taiwan. Overall, 7.3% of older people had used TCM within the previous month. People with a history of heart disease (OR 1.62, 95% CI 1.24-2.12), use of folk therapy (OR 3.16, 95% CI 2.00-4.99), and purchase of non-prescribed Chinese herbal medicine (OR 2.08, 95% CI 1.48-2.91) were more likely to use TCM than the comparison group. However, age ≥80 years (OR 0.48, 95% CI 0.31-0.72) and previous hospitalization (OR 0.59, 95% CI 0.41-0.85) were associated with the reduced use of TCM. CONCLUSION: From 2001-2017, the use of TCM increased in the older population in Taiwan. The use of folk medicine and purchase of non-prescribed Chinese herbal medicine were significant predictors for the use of TCM.

Characteristics and treatment response of polypoidal choroidal vasculopathy in highly myopic eyes.

BACKGROUND: To compare the characteristics and treatment responses of polypoidal choroidal vasculopathy (PCV) between highly myopic and non-highly myopic eyes. METHODS: This retrospective cohort study included patients diagnosed with PCV at the clinic of National Taiwan University Hospital between 2013 and 2019. The diseased eyes were grouped per refractive error and axial length at diagnosis. Imaging data were used to retrieve the PCV characteristics, and electronic medical records were used to retrieve the treatment responses. RESULTS: Among 116 eyes with PCV, 11 eyes of 10 patients were highly myopic; seven of these patients were women. All highly myopic eyes showed a thin subfoveal choroid, while three eyes had a pachychoroid phenotype with significant focal choroidal thickening. After treatment with either intravitreal anti-vascular endothelial growth factor (VEGF) injections, photodynamic therapy (PDT), or both, best-corrected visual acuity was better in the high-myopia group at 1 year. Visual acuity at presentation and the presence of feeder vessels were found to be predictors of the visual outcome. CONCLUSIONS: In this study we reported, to the best of our knowledge, the largest cohort of PCV in highly myopic eyes to date. Female predominance, lower incidence of subretinal haemorrhage, and a thin choroid with a focal pachychoroid phenotype were found to characterise PCV in highly myopic eyes. Visual acuity transiently improved after either anti-VEGF monotherapy or combination therapy with PDT.

A modified surgical technique of fibrin glue-assisted double bipedicle conjunctival flaps for patients with ocular surface diseases.

This study aimed to describe and investigate the surgical outcome and complications of fibrin glue-assisted double bipedicle conjunctival flaps (CFs) (FADCOF), an alternative surgical technique that restores a stable ocular surface in patients with painful blinding ocular surface disease combined with a shortage of bulbar conjunctiva. Six eyes of six patients with painful blinding ocular surface disease were enrolled in this study. All patients had inadequate superior or inferior conjunctiva tissue to cover the whole corneal surface owing to previous surgeries or ocular surface diseases. These patients received FADCOF between 2009 and 2019. The main outcome included surgical success rate, visual analog scale (VAS) pain score, ocular inflammation score, and postoperative complications. Surgical success was defined as resolution of initial ocular complaints and restoration of a stable ocular surface with no flap melting, retraction, or dehiscence resulting in re-exposure of the corneal surface. All of the six eyes (100%) achieved surgical success. All patients reported significant improvement in subjective symptoms and complete resolution of ocular pain after the surgery (VAS pain score: 6.5 ± 0.5 preoperatively to 0.0 ± 0.0 at 1 month). Ocular inflammation score decreased significantly from a presurgical value of 1.83 ± 0.69 to 0.33 ± 0.47 1 month after the surgery. No postoperative complication was found during the long-term follow-up (range: 12-82 months). FADCOF is a reliable alternative for patients with painful blinding ocular surface diseases unsuitable for single total CF surgery. This surgical technique yields fast ocular surface stabilization, satisfactory recovery, and low complication rates.

Characteristics and response of subretinal hyperreflective material to anti-vascular endothelial growth factor in myopic choroidal neovascularization.

This retrospective study evaluated the characteristics and response of subretinal hyperreflective material (SHRM) to anti-vascular endothelial growth factor (VEGF) treatment in eyes with myopic choroidal neovascularization (CNV). The visual acuity (VA) was assessed at 3, 6, and 12 months after initiating anti-VEGF treatment in 116 patients (119 eyes) with SHRM and myopic CNV. Multimodal imaging, including color fundus photography, fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), were performed. We compared type 2 neovascularization (NV) (n = 64), subretinal hyperreflective exudation (SHE) (n = 37), NV with hemorrhage (n = 15), and fibrosis (n = 3). The type 2 NV group, and NV with hemorrhage groups showed significant VA improvement after 12 months of treatment (p < 0.05 in both groups); the SHE group failed to show improvement (p = 0.366). All groups showed a significant reduction in central foveal thickness after 12 months of treatment (all p < 0.05). The SHE group had a significantly higher incidence of interrupted ellipsoid zone than the other groups (p < 0.05). Myopic CNV can present as SHRM on OCT-A. Visual prognoses vary in different SHRM types. OCT-A and FA may help predict the outcomes of different subtypes of myopic CNV. SHE is predictive of outer retinal layer atrophy in patients with various SHRM types.

Comparison of Refractive Outcomes in Patients with Highly Myopic Versus Non-highly Myopic Eyes Undergoing Phacovitrectomy.

INTRODUCTION: Combined phacovitrectomy is gaining popularity due to efficiency and immediate visual improvement. However, concerns regarding erroneous intraocular lens (IOL) calculation in combination surgery are increasing, such as myopic shift owing to a thick macula and consequent underestimation of the axial length. Therefore, this study aimed to compare the refractive outcomes of combined phacovitrectomy in patients with highly myopic and non-highly myopic eyes. METHODS: A retrospective chart review was performed on patients who received combined phacoemulsification, intraocular lens implantation, and small gauge pars plana vitrectomy for cataract and macular pathologies in highly myopic and non-highly myopic eyes. Pre- and postoperative evaluation and ocular parameters were recorded, and analyses were performed using the Student's t test and regression analysis. RESULTS: A total of 133 patients with macular pathologies, including myopic tractional maculopathy, macular hole, and epiretinal membrane, were enrolled. SRK II or SRK/T models were used for calculating IOL. The mean absolute error of refraction change was 0.65 D; 83.5% of patients were within 1-D error, 57.9% within 0.5-D error, and 35.3% within 0.25-D error, with SRK/T showing better precision and yielding more myopic shift. Furthermore, the predictive accuracy of SRK II or SRK/T was better in patients with non-highly myopic eyes. Moreover, Barrett's universal II formula was not superior to SRK II or SRK/T in the prediction of postoperative refractive error (p = 0.48). CONCLUSION: Refractive outcomes were satisfactory in the cohort of patients with highly myopic eyes. The combined implementation of SRK II and SRK/T was not inferior to Barrett's universal II formula in predicting satisfactory refractive outcomes. Combination surgery can be an option for patients with both cataract and macular pathologies.

Correlation of Visual Acuity and Outer Retinal Thickness in Myopic Atrophic Maculopathy: A Retrospective Review.

INTRODUCTION: Myopic atrophic maculopathy is prevalent among patients with pathologic myopia and frequently leads to relentless vision loss. Several grading systems were established to facilitate the understanding of myopic atrophic maculopathy. However, the anatomical details in different stages of myopic maculopathy are so far not clearly elucidated. This study aims to investigate the visual acuity and retinal sublayer features in highly myopic eyes with varying severities of myopic atrophic maculopathy (MAM). METHODS: The clinical records of 111 consecutive patients (158 eyes) with high myopia (refractive error ≤ -6.0 D and axial length ≥ 26.0 mm) were reviewed. Fundus photography, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) were measured. MAM was graded according to the META-analysis for Pathologic Myopia (META-PM) classification system. Myopic choroidal neovascularization (mCNV) and dome-shaped macula (DSM) were also investigated. RESULTS: Among the 158 eyes, 18 (11%), 21(13%), 24 (15%), 25 (16%), 23 (15%), and 24 (15%) had tessellated fundus, diffuse chorioretinal atrophy, diffuse chorioretinal atrophy with DSM, patchy atrophy, patchy atrophy with DSM, and MAM with mCNV, respectively. A total of 23 (15%) eyes had macular atrophy without mCNV. Progressive thinning in the Henle's fiber and outer nuclear layers, myoid and ellipsoid zone (MEZ), outer segment (OS), and interdigitation zone and retinal pigmented epithelium based on the severity of MAM (p-value < 0.001) was found. MEZ and OS were most significantly reduced in thickness (p-value < 0.001). The presence of mCNV demonstrated significant outer retinal layer thinning compared with that of the tessellated fundus (p-value = 0.031). Patchy atrophy with DSM showed statistically poorer BCVA compared with that without (p-value = 0.008). CONCLUSION: Visual acuity and outer retinal sublayer characteristics were correlated with the severity of MAM. Outer retinal sublayer analysis by spectrum-domain OCT shed some light on the mechanisms of MAM progression.

Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma.

Objective: Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next-generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases. Methods: Thirty-three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression-free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases. Results: The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non-acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway (CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P = 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, GZMH, GZMK, AIM2 and CTLA4, were found to be associated with both PFS and OS. Conclusion: Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.

Investigation of hole transport layer in relation to the properties of organic solar cells.

Organic solar cells based on a blend of copper phthalocyanine and bulk fullerene are fabricated with a double hole transport layer system. The double hole transport layer was composed of poly3,4-ethylenedioxythiophene:polystyrenesulfonate, and copper phthalocyanine and inserted between the anode and active layer. The double hole transport layer system utilizes advantages of both layer. The poly3,4-ethylenedioxythiophene:polystyrenesulfonate layer modifies the surface morphology of the ITO anode and the copper phthalocyanine layer enhances hole transport. In order to enhance the conductivity of the modification layer, the optimal amount of glycerol is doped into poly3,4-ethylenedioxythiophene:polystyrenesulfonate. Furthermore, the photovoltaic characteristics are further improved. Insertion of the double hole transport layer with a 4 nm-thick copper phthalocyanine layer resulted in open circuit voltage, short current, and power conversion efficiency as high as 0.46 V, 8.8 mA/cm2 and 1.37%, respectively.