Publications by authors named "Hsin-Yu Kuo"

28 Publications

  • Page 1 of 1

Cubic-Phase Metasurface for Three-Dimensional Optical Manipulation.

Nanomaterials (Basel) 2021 Jun 30;11(7). Epub 2021 Jun 30.

Department of Physics, National Taiwan University, Taipei 10617, Taiwan.

The optical tweezer is one of the important techniques for contactless manipulation in biological research to control the motion of tiny objects. For three-dimensional (3D) optical manipulation, shaped light beams have been widely used. Typically, spatial light modulators are used for shaping light fields. However, they suffer from bulky size, narrow operational bandwidth, and limitations of incident polarization states. Here, a cubic-phase dielectric metasurface, composed of GaN circular nanopillars, is designed and fabricated to generate a polarization-independent vertically accelerated two-dimensional (2D) Airy beam in the visible region. The distinctive propagation characteristics of a vertically accelerated 2D Airy beam, including non-diffraction, self-acceleration, and self-healing, are experimentally demonstrated. An optical manipulation system equipped with a cubic-phase metasurface is designed to perform 3D manipulation of microscale particles. Due to the high-intensity gradients and the reciprocal propagation trajectory of Airy beams, particles can be laterally shifted and guided along the axial direction. In addition, the performance of optical trapping is quantitatively evaluated by experimentally measured trapping stiffness. Our metasurface has great potential to shape light for compact systems in the field of physics and biological applications.
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http://dx.doi.org/10.3390/nano11071730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308168PMC
June 2021

Assessment of the changes in retention and surface topography of attachments for maxillary 4-implant-retained overdentures.

J Prosthet Dent 2021 Jun 11. Epub 2021 Jun 11.

Clinical Professor, Department of Prosthodontics, College of Dental Medicine, Columbia University, New York, NY.

Statement Of Problem: Restoring the edentulous maxilla with an implant-retained overdenture (IRO) can present a challenge because of increased implant divergence and the added wear of the implant abutments and attachments. However, knowledge pertaining to the degree of implant divergence and its effects on the wear pattern of the implant attachments is lacking.

Purpose: The purpose of this in vitro study was to investigate the change in the retention and wear characteristics of unsplinted abutments and attachments when used to retain a maxillary 4-implant palateless complete removable overdenture with different implant angulations.

Material And Methods: Three groups of specimens of 0-, 15-, and 30-degree implant angulations were evaluated, each with 7 specimens. The retention of specimens was recorded after aging cycles equivalent to 1, 2.5, and 6 years of use. The surface of the attachments was examined with light and scanning electron microscope (SEM).

Results: Increasing the interimplant divergence improved the initial retention. After 1 year of use, retention of the 15- and 30-degree groups was significantly higher than that of the 0-degree group (P<.05). No significant difference in retention was found between the 15- and 30-degree groups (P>.05). After 2.5 and 6 years of use, no significant difference in retention was noted between groups (P>.05). Under light and SEM examination, the wear of the abutments and attachments was related to the interimplant divergence.

Conclusions: The initial retention of single attachments increased significantly as the implant divergence increased. The retention of the15- and 30-degree groups was significantly higher than that of the 0-degree group after 1 year of use. No significant difference in retention was found after 2.5 and 6 years, regardless of implant angulation.
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http://dx.doi.org/10.1016/j.prosdent.2021.05.002DOI Listing
June 2021

Varifocal Metalens for Optical Sectioning Fluorescence Microscopy.

Nano Lett 2021 06 7;21(12):5133-5142. Epub 2021 Jun 7.

Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan.

Fluorescence microscopy with optical sectioning capabilities is extensively utilized in biological research to obtain three-dimensional structural images of volumetric samples. Tunable lenses have been applied in microscopy for axial scanning to acquire multiplane images. However, images acquired by conventional tunable lenses suffer from spherical aberration and distortions. Here, we design, fabricate, and implement a dielectric Moiré metalens for fluorescence imaging. The Moiré metalens consists of two complementary phase metasurfaces, with variable focal length, ranging from ∼10 to ∼125 mm at 532 nm by tuning mutual angles. In addition, a telecentric configuration using the Moiré metalens is designed for high-contrast multiplane fluorescence imaging. The performance of our system is evaluated by optically sectioned images obtained from HiLo illumination of fluorescently labeled beads, as well as ex vivo mice intestine tissue samples. The compact design of the varifocal metalens may find important applications in fluorescence microscopy and endoscopy for clinical purposes.
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http://dx.doi.org/10.1021/acs.nanolett.1c01114DOI Listing
June 2021

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis.

Cancer Immunol Immunother 2021 Jul 6;70(7):1929-1937. Epub 2021 Jan 6.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2-12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child-Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.
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http://dx.doi.org/10.1007/s00262-020-02845-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195886PMC
July 2021

Novel upper gastrointestinal monitoring system to track upper gastrointestinal bleeding: A pilot study.

Endosc Int Open 2020 Dec 17;8(12):E1811-E1816. Epub 2020 Nov 17.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

 Early detection of upper gastrointestinal (UGI) rebleeding is not easy by observing clinical symptoms. We developed a novel UGI monitoring system and aimed to test its feasibility of continuous tracking of UGI bleeding.  A prospective study was conducted on patients with moderate to high risk of rebleeding. The UGI monitoring system was installed to monitor their gastric contents. It would alarm if rebleeding was suspected and the physician could review the images to make a further decision. The patient's comfort level was also evaluated. Sixteen patients were enrolled. Rebleeding occurred in one patient and was detected by this system more than 5 hours earlier than with clinical symptoms. The interobserver reliability for reviewing the images to define the blood clearance in the stomach was excellent (intraclass correlation coefficient 0.79-0.96). The comfort level assessed by patients was 1.90 ± 1.39 (on the scale of 0-5).  This pilot study demonstrated the potential of this UGI monitoring system for early detection of rebleeding.
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http://dx.doi.org/10.1055/a-1266-3501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671761PMC
December 2020

Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen.

Eur J Clin Pharmacol 2020 Nov 27;76(11):1581-1589. Epub 2020 Jun 27.

Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Purpose: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection.

Methods: We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy.

Results: The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025).

Conclusion: Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.
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http://dx.doi.org/10.1007/s00228-020-02938-5DOI Listing
November 2020

Metalens-array-based high-dimensional and multiphoton quantum source.

Science 2020 06;368(6498):1487-1490

Department of Electronic and Information Engineering, The Hong Kong Polytechnic University, Hong Kong.

The development of two-dimensional metasurfaces has shown great potential in quantum-optical technologies because of the excellent flexibility in light-field manipulation. By integrating a metalens array with a nonlinear crystal, we demonstrate a 100-path spontaneous parametric down-conversion photon-pair source in a 10 × 10 array, which shows promise for high-dimensional entanglement and multiphoton-state generation. We demonstrate two-, three- and four-dimensional two-photon path entanglement with different phases encoded by metalenses with fidelities of 98.4, 96.6, and 95.0%, respectively. Furthermore, four-photon and six-photon generation is observed with high indistinguishability of photons generated from different metalenses. Our metalens-array-based quantum photon source is compact, stable, and controllable, indicating a new platform for integrated quantum devices.
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http://dx.doi.org/10.1126/science.aba9779DOI Listing
June 2020

Impact of Immune Checkpoint Inhibitors with or without a Combination of Tyrosine Kinase Inhibitors on Organ-Specific Efficacy and Macrovascular Invasion in Advanced Hepatocellular Carcinoma.

Oncol Res Treat 2020 26;43(5):211-220. Epub 2020 Feb 26.

Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan,

Introduction: The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response.

Objective: This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC).

Methods: We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis.

Results: We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS.

Conclusions: PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders.
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http://dx.doi.org/10.1159/000505933DOI Listing
September 2020

Spectral tomographic imaging with aplanatic metalens.

Light Sci Appl 2019 6;8:99. Epub 2019 Nov 6.

1National Laboratory of Solid State Microstructures, Key Laboratory of Intelligent Optical Sensing and Integration, Jiangsu Key Laboratory of Artificial Functional Materials, College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210093 China.

Tomography is an informative imaging modality that is usually implemented by mechanical scanning, owing to the limited depth-of-field (DOF) in conventional systems. However, recent imaging systems are working towards more compact and stable architectures; therefore, developing nonmotion tomography is highly desirable. Here, we propose a metalens-based spectral imaging system with an aplanatic GaN metalens (NA = 0.78), in which large chromatic dispersion is used to access spectral focus tuning and optical zooming in the visible spectrum. After the function of wavelength-switched tomography was confirmed on cascaded samples, this aplanatic metalens is utilized to image microscopic frog egg cells and shows excellent tomographic images with distinct DOF features of the cell membrane and nucleus. Our approach makes good use of the large diffractive dispersion of the metalens and develops a new imaging technique that advances recent informative optical devices.
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http://dx.doi.org/10.1038/s41377-019-0208-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834576PMC
November 2019

Risks of angled implant placement on posterior mandible buccal/lingual plated perforation: A virtual immediate implant placement study using CBCT.

J Dent Sci 2019 Sep 20;14(3):234-240. Epub 2019 Mar 20.

Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background/purpose: Immediate implant placement has been considered to be a successful treatment procedure. The bone plate perforation (BPP) may be one of severe complication and potentially life-threatening situation. The aim of this virtual study is to evaluate the influences of angled implant insertion on BPP during immediate implant installation in the posterior mandible.

Materials And Methods: Cone beam computed tomography images of 488 posterior teeth from 61 patients were selected. Virtual immediate implant placement (VIIP) was performed at each posterior tooth following the appropriate axis with the prosthetic-driven planning and different deviation angles of 3-, 6-, or 9-degree. BPP was then examined from cross-sectional images obtained. Furthermore, the relation of lingual bony morphology and BPP were also determined.

Results: The incidence of buccal and lingual BPP increased as the deviation angle increased in posterior mandible area. Incidence of lingual BPP was significantly influenced by angular deviation and type of lingual bony morphology after adjusting for age, gender, tooth type, and right/left side. An increase in incidence odds of over 6-fold (OR = 6.583) was noted for placements angled by 9° compared with placements made without angulation, and an increase in incidence odds of over 3-fold (OR = 3.622) was noted for teeth with the undercut-type lingual morphology compared with the other types.

Conclusion: The present Results indicate that accurate selection of the implant insertion angle and full awareness of the bony anatomy at the implant recipient site are essential to prevent BPP in the posterior mandible.
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http://dx.doi.org/10.1016/j.jds.2019.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739299PMC
September 2019

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

Surg Endosc 2020 04 20;34(4):1592-1601. Epub 2019 Jun 20.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy.

Methods: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4-28th day after the first bleeding episode.

Results: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01).

Conclusions: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.
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http://dx.doi.org/10.1007/s00464-019-06919-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223755PMC
April 2020

Spasmolytic polypeptide-expressing metaplasia associated with higher expressions of miR-21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives.

Helicobacter 2019 Jun 16;24(3):e12578. Epub 2019 Apr 16.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.

Background And Aims: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication.

Methods: We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication.

Results: GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P < 0.01) than controls. The tissue miR-21, 155, and 223 in antrum were higher in cases with SPEM than in those without SPEM (P <= 0.05). There was similar SPEM reversibility after H pylori eradication between GCF subjects and controls (72% vs 69%, P = 0.852). In the SPEM regressed cases, tissue miR-21, 155, and 223 decreased after H pylori eradication (P < 0.05).

Conclusion: The H pylori-infected GCF subjects were prone to have SPEM with higher tissues miR-21, 155, and 223 expressions. H pylori eradication can result in a 70% SPEM regression, accompanied by a decline in miR-21, 155, and 233 expression levels.
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http://dx.doi.org/10.1111/hel.12578DOI Listing
June 2019

Achromatic metalens array for full-colour light-field imaging.

Nat Nanotechnol 2019 03 21;14(3):227-231. Epub 2019 Jan 21.

Department of Physics, National Taiwan University, Taipei, Taiwan.

A light-field camera captures both the intensity and the direction of incoming light. This enables a user to refocus pictures and afterwards reconstruct information on the depth of field. Research on light-field imaging can be divided into two components: acquisition and rendering. Microlens arrays have been used for acquisition, but obtaining broadband achromatic images with no spherical aberration remains challenging. Here, we describe a metalens array made of gallium nitride (GaN) nanoantennas that can be used to capture light-field information and demonstrate a full-colour light-field camera devoid of chromatic aberration. The metalens array contains an array of 60 × 60 metalenses with diameters of 21.65 μm. The camera has a diffraction-limited resolution of 1.95 μm under white light illumination. The depth of every object in the scene can be reconstructed slice by slice from a series of rendered images with different depths of focus. Full-colour, achromatic light-field cameras could find applications in a variety of fields such as robotic vision, self-driving vehicles and virtual and augmented reality.
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http://dx.doi.org/10.1038/s41565-018-0347-0DOI Listing
March 2019

H. pylori isolates with amino acid sequence polymorphisms as presence of both HtrA-L171 & CagL-Y58/E59 increase the risk of gastric cancer.

J Biomed Sci 2019 Jan 5;26(1). Epub 2019 Jan 5.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59.

Methods: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing.

Results: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1-6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001).

Conclusions: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.
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http://dx.doi.org/10.1186/s12929-019-0498-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321681PMC
January 2019

A broadband achromatic metalens in the visible.

Nat Nanotechnol 2018 03 29;13(3):227-232. Epub 2018 Jan 29.

Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan.

Metalenses consist of an array of optical nanoantennas on a surface capable of manipulating the properties of an incoming light wavefront. Various flat optical components, such as polarizers, optical imaging encoders, tunable phase modulators and a retroreflector, have been demonstrated using a metalens design. An open issue, especially problematic for colour imaging and display applications, is the correction of chromatic aberration, an intrinsic effect originating from the specific resonance and limited working bandwidth of each nanoantenna. As a result, no metalens has demonstrated full-colour imaging in the visible wavelength. Here, we show a design and fabrication that consists of GaN-based integrated-resonant unit elements to achieve an achromatic metalens operating in the entire visible region in transmission mode. The focal length of our metalenses remains unchanged as the incident wavelength is varied from 400 to 660 nm, demonstrating complete elimination of chromatic aberration at about 49% bandwidth of the central working wavelength. The average efficiency of a metalens with a numerical aperture of 0.106 is about 40% over the whole visible spectrum. We also show some examples of full-colour imaging based on this design.
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http://dx.doi.org/10.1038/s41565-017-0052-4DOI Listing
March 2018

Peptide Arrays: Development and Application.

Anal Chem 2018 01 5;90(1):266-282. Epub 2017 Dec 5.

Institute of Chemical Biology and Nanomedicine, Hunan University , Changsha 410082, China.

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http://dx.doi.org/10.1021/acs.analchem.7b04380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526727PMC
January 2018

Osteopontin polymorphism increases gastric precancerous intestinal metaplasia susceptibility in Helicobacter pylori infected male.

Future Oncol 2017 Jul 7;13(16):1415-1425. Epub 2017 Jul 7.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Aim: Whether genetic polymorphisms of osteopontin (OPN) coding gene, SPP1, determine the risk of gastric precancerous intestinal metaplasia (IM) in Helicobacter pylori infected patients.

Patients & Methods: Helicobacter pylori infected patients (100 with and 210 without IM) were recruited to evaluate the associations of SPP1 promoter polymorphisms with gastric IM and adjusted for age, sex and smoking. Gastric OPN expression and inflammation were evaluated by immunohistochemistry, and haemotoxylin and eosin stain.

Results: Only in males, but not females, carriage of both GG genotype at rs11730059 and C-G-C haplotype at rs6833161-rs2853744-rs11730582 significantly increased the IM risk (OR: 4.92; 95% CI: 1.65-14.65; p = 0.004). Nearly 87.5% of males with IM carried risky genotype or haplotype. Carriers of the risky genotype or haplotype also had increased gastric OPN expression (p = 0.038) and inflammation (p = 0.007).

Conclusion: SPP1 polymorphisms predispose to IM development in H. pylori infected males.
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http://dx.doi.org/10.2217/fon-2017-0006DOI Listing
July 2017

The corpus-predominant gastritis index can be an early and reversible marker to identify the gastric cancer risk of Helicobacter pylori-infected nonulcer dyspepsia.

Helicobacter 2017 Aug 22;22(4). Epub 2017 Mar 22.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: Corpus-predominant gastritis index (CGI) is an early histological marker to identify Helicobacter pylori-infected gastric cancer relatives at risk of cancer. This study validated whether CGI is more prevalent in H. pylori-infected nonulcer dyspepsia (NUD) subjects than in duodenal ulcer (DU) controls and whether it is reversible after H. pylori eradication or is correlated with noninvasive biomarkers.

Materials And Methods: In this longitudinal cohort study, 573 H. pylori-infected subjects were enrolled, including 349 NUD and 224 DU. Gastric specimens were provided to assess CGI, spasmolyic polypeptide-expressing metaplasia (SPEM), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM). Serum pepsinogen I and II levels were assessed using enzyme-linked immunosorbent assay. CGI subjected were followed up at least 1 year after H. pylori eradication.

Results: NUD subjects had higher prevalence rates of CGI (47.0% vs 29.9%, P<.001) and OLGIM stages III-IV (24.1% vs 15.2%, P=.01) than controls. CGI was highly prevalent in NUD subjects after the age of 40, which was 10 years earlier than atrophic gastritis and intestinal metaplasia. NUD subjects with CGI had higher risk of SPEM (OR 2.86, P<.001) and lower serum pepsinogen I/II ratios (P<.001) than those without CGI. Serum pepsinogen I/II ratios <9 could predict CGI modestly (AUROC 0.69, 95% CI: 0.63-0.74). CGI was regressed after eradication (P<.001).

Conclusions: CGI was more prevalent in H. pylori-infected NUD subjects than in controls, was correlated with SPEM, and may serve as a marker earlier than OLGIM to indicate risk of gastric cancer. Moreover, CGI could be regressed after eradication.
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http://dx.doi.org/10.1111/hel.12385DOI Listing
August 2017

Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

Biomaterials 2016 10 28;103:207-218. Epub 2016 Jun 28.

Institute of Pharmacology, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, ROC; Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 112, Taiwan, ROC; Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Taipei, 115, Taiwan, ROC. Electronic address:

Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD.
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http://dx.doi.org/10.1016/j.biomaterials.2016.06.060DOI Listing
October 2016

Serum Level of Trefoil Factor 2 can Predict the Extent of Gastric Spasmolytic Polypeptide-Expressing Metaplasia in the H. pylori-Infected Gastric Cancer Relatives.

Helicobacter 2017 Feb 25;22(1). Epub 2016 May 25.

Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background & Aims: Gastric cancer has familial clustering in incidence, and the familial relatives of gastric cancer sufferers are prone to have spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM) after H. pylori infection. This study tested whether serum pepsinogen I/II and trefoil factor family (TFF) proteins can predict SPEM or IM in the H. pylori-infected relatives of patients with gastric cancer.

Methods: We prospectively enrolled 119 H. pylori-infected relatives of gastric cancer patients of noncardiac gastric cancer patients, who then received panendoscopy to obtain gastric biopsy to define the presence of corpus gastritis index (CGI), SPEM, and IM. The advanced SPEM in histology was defined by TFF2 immunohistochemistry. Each patient also had checkups of serum TFF2, TFF3, and pepsinogen I/II by enzyme-linked immunosorbent assay (ELISA).

Results: The 119 H. pylori-infected relatives included 61 with SPEM, and 34 with IM. The presence of either IM or SPEM was not related to the serum TFF2, TFF3, and pepsinogen I/II levels (p > .05). Serum TFF2 levels were higher in relatives with CGI who also had advanced SPEM (p = .032). For relatives without CGI, the elevated serum TFF2 levels correlated with higher H. pylori density and more severe gastritis in antrum (p = .001).

Conclusion: The serum TFF2 level cannot predict SPEM or IM in H. pylori-infected relatives of patients with gastric cancer. For H. pylori-infected relatives with CGI, serum TFF2 levels may predict the advanced severity of SPEM. Elevated serum TFF2 levels may indicate severe H. pylori-related inflammation, at risk of development or progression of SPEM in relatives without CGI.
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http://dx.doi.org/10.1111/hel.12320DOI Listing
February 2017

SIRT1 is a critical regulator of K562 cell growth, survival, and differentiation.

Exp Cell Res 2016 05 13;344(1):40-52. Epub 2016 Apr 13.

Department of Chemical and Biological Engineering; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, United States. Electronic address:

Inhibition of histone deacetylases (HDACi) has emerged as a promising approach in the treatment of many types of cancer, including leukemias. Among the HDACs, Class III HDACs, also known as sirtuins (SIRTs), are unique in that their function is directly related to the cell's metabolic state through their dependency on the co-factor NAD(+). In this study, we examined the relation between SIRTs and the growth, survival, and differentiation of K562 erythroleukemia cells. Using a mass spectrometry approach we previously developed, we show that SIRT expression and deacetylase activity in these cells changes greatly with differentiation state (undifferentiated vs. megakaryocytic differentiation vs. erythroid differentiation). Moreover, SIRT1 is crucially involved in regulating the differentiation state. Overexpression of wildtype (but not deacetylase mutant) SIRT1 resulted in upregulation of glycophorin A, ~2-fold increase in the mRNA levels of α, γ, ε, and ζ-globins, and spontaneous hemoglobinization. Hemin-induced differentiation was also enhanced by (and depended on) higher SIRT1 levels. Since K562 cells are bipotent, we also investigated whether SIRT1 modulation affected their ability to undergo megakaryocytic (MK) differentiation. SIRT1 was required for commitment to the MK lineage and subsequent maturation, but was not directly involved in polyploidization of either K562 cells or an already-MK-committed cell line, CHRF-288-11. The observed blockage in commitment to the MK lineage was associated with a dramatic decrease in the formation of autophagic vacuoles, which was previously shown to be required for K562 cell MK commitment. Autophagy-associated conversion of the protein LC3-I to LC3-II was greatly enhanced by overexpression of wildtype SIRT1, further suggesting a functional connection between SIRT1, autophagy, and MK differentiation. Based on its clear effects on autophagy, we also examined the effect of SIRT1 modulation on stress responses. Consistent with results of prior studies, we found that SIRT1 silencing modestly promoted drug-induced apoptosis, while overexpression was protective. Furthermore, pan-SIRT inhibition mediated by nicotinamide pre-treatment substantially increased imatinib-induced apoptosis. Altogether, our results suggest a complex role for SIRT1 in regulating many aspects of K562 cell state and stress response. These observations warrant further investigation using normal and leukemic primary cell models. We further suggest that, ultimately, a well-defined mapping of HDACs to their substrates and corresponding signaling pathways will be important for optimally designing HDACi-based therapeutic approaches.
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http://dx.doi.org/10.1016/j.yexcr.2016.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879089PMC
May 2016

Preparation and physicochemical properties of whole-bean soymilk.

J Agric Food Chem 2014 Jan 10;62(3):742-9. Epub 2014 Jan 10.

Graduate Institute of Food Science and Technology, National Taiwan University , 1 Roosevelt Road, Section 4, Taipei 10617, Taiwan.

Whole-bean soymilk has been prepared by using media-milling. Some characteristics of media-milled soymilk have been determined and compared with filtered soymilk (similar to commercial ones) and whole-bean soymilk prepared by blending. There existed particles in the nano/submicrometer scale in both media-milled and filtered soymilk. The particles in blended soymilk were greater than 1 μm. Media-milled soymilk was the most stable among three samples, even after autoclaving. Solid recovery (98.44 ± 0.16%), viscosity (160.59 ± 4.26 cps), dietary fiber (22.68 ± 0.97% on dry basis), total polyphenol recovery (95.15 ± 7.09%), and isoflavone content (4.42 ± 0.03 mg/g dry solid) of media-milled samples were greater than those of filtered ones. Aglycones, the most bioactive form of isoflavone, in autoclaved media-milled soymilk were more than 2-fold those in autoclaved filtered soymilk. With almost no okara generated, the media-milled soymilk retained fiber in soybeans which would be beneficial to human health.
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http://dx.doi.org/10.1021/jf404465wDOI Listing
January 2014

Profiling deacetylase activities in cell lysates with peptide arrays and SAMDI mass spectrometry.

Anal Chem 2013 Nov 11;85(22):10635-10642. Epub 2013 Oct 11.

Departments of Biomedical Engineering, Chemistry, Cell & Molecular Biology, Northwestern University, Evanston, Illinois 60208.

The development of arrays that can profile molecular activities in cells is important to understanding signaling pathways in normal and pathological settings. While oligonucleotide arrays are now routinely used to profile global gene expression, there is still a lack of tools for profiling enzyme activities in cell lysates. This paper describes the combination of peptide arrays formed on self-assembled monolayers and mass spectrometry to provide a label-free approach for identifying patterns of enzyme activities in cell lysates. The approach is demonstrated by profiling lysine deacetylase (KDAC) activities in cell lysates of the CHRF megakaryocytic (Mk) cell line. Class-specific deacetylase inhibitors were used to show that terminal Mk differentiation of CHRF cells is marked by a pronounced decrease in sirtuin activity and by little change in activity of KDACs 1-11. This work establishes a platform that can be used to identify changes in global activity profiles of cell lysates for a wide variety of enzymatic activities.
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http://dx.doi.org/10.1021/ac402614xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912874PMC
November 2013

Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.

Science 2013 Nov 19;342(6158):1243417. Epub 2013 Sep 19.

Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Circadian clocks are self-sustained cellular oscillators that synchronize oxidative and reductive cycles in anticipation of the solar cycle. We found that the clock transcription feedback loop produces cycles of nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, adenosine triphosphate production, and mitochondrial respiration through modulation of mitochondrial protein acetylation to synchronize oxidative metabolic pathways with the 24-hour fasting and feeding cycle. Circadian control of the activity of the NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms in the acetylation and activity of oxidative enzymes and respiration in isolated mitochondria, and NAD(+) supplementation restored protein deacetylation and enhanced oxygen consumption in circadian mutant mice. Thus, circadian control of NAD(+) bioavailability modulates mitochondrial oxidative function and organismal metabolism across the daily cycles of fasting and feeding.
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http://dx.doi.org/10.1126/science.1243417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963134PMC
November 2013

Cannabinoid receptors as therapeutic targets for dialysis-induced peritoneal fibrosis.

Am J Nephrol 2013 4;37(1):50-8. Epub 2013 Jan 4.

Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Long-term exposure to bioincompatible peritoneal dialysis solutions is frequently complicated with peritoneal fibrosis and ultrafiltration failure. As cannabinoid receptor (CBR) ligands have been reported to be beneficial to ameliorate the process of liver fibrosis, we strove to investigate their therapeutic potential to prevent peritoneal fibrosis.

Methods: We used the rat model of peritoneal fibrosis induced by intraperitoneal injection of methylglyoxal and in vitro mesothelial cell culture to test the effects of CBR ligands, including the type 1 CBR (CB(1)R) antagonist and the type 2 CBR (CB(2)R) agonist.

Results: In the methylglyoxal model, both intraperitoneal CB(1)R antagonist (AM281) and CB(2)R agonist (AM1241) treatment significantly ameliorated peritoneal fibrosis. In addition, CB(1)R antagonist was able to alleviate TGF-β(1)-induced dedifferentiation of mesothelial cells and to maintain epithelial integrity in vitro.

Conclusions: Intraperitoneal administration of CBR ligands (CB(1)R antagonist and CB(2)R agonist) offers a potential therapeutic strategy to reduce dialysis-induced peritoneal fibrosis and to prolong the peritoneal survival in peritoneal dialysis patients.
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http://dx.doi.org/10.1159/000345726DOI Listing
August 2013

Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in leukemia cells.

Haematologica 2013 May 14;98(5):729-38. Epub 2012 Sep 14.

Institute of Biopharmaceutical Sciences, National Yang-Ming Universit, Taipei, Taiwan.

The multiple cellular targets affected by proteasome inhibition implicate a potential role for bortezomib, a first-in-class proteasome inhibitor, in enhancing antitumor activities in hematologic malignancies. Here, we examined the antitumor activity and drug targets of bortezomib in leukemia cells. Human leukemia cell lines were used for in vitro studies. Drug efficacy was evaluated by apoptosis assays and associated molecular events assessed by Western Blot. Gene silencing was performed by small interference RNA. Drug was tested in vivo in xenograft models of human leukemia cell lines and in primary leukemia cells. Clinical samples were assessed by immunohistochemical staining. Bortezomib differentially induced apoptosis in leukemia cells that was independent of its proteasome inhibition. Cancerous inhibitor of protein phosphatase 2A, a cellular inhibitor of protein phosphatase 2A, mediated the apoptotic effect of bortezomib. Bortezomib increased protein phosphatase 2A activity in sensitive leukemia cells (HL-60 and KG-1), but not in resistant cells (MOLT-3 and K562). Bortezomib's downregulation of cancerous inhibitor of protein phosphatase 2A and phospho-Akt correlated with its drug sensitivity. Furthermore, cancerous inhibitor of protein phosphatase 2A negatively regulated protein phosphatase 2A activity. Ectopic expression of CIP2A up-regulated phospho-Akt and protected HL-60 cells from bortezomib-induced apoptosis, whereas silencing CIP2A overcame the resistance to bortezomib-induced apoptosis in MOLT3 and K562 cells. Importantly, bortezomib exerted in vivo antitumor activity in HL-60 xenografted tumors and induced cell death in some primary leukemic cells. Cancerous inhibitor of protein phosphatase 2A was expressed in leukemic blasts from bone marrow samples. Cancerous inhibitor of protein phosphatase 2A plays a major role in mediating bortezomib-induced apoptosis in leukemia cells.
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http://dx.doi.org/10.3324/haematol.2011.050187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640117PMC
May 2013

The daily lives of adolescents with an autism spectrum disorder: discretionary time use and activity partners.

Autism 2011 Sep 22;15(5):579-99. Epub 2011 Jun 22.

Boston University, Massachusetts, USA.

This study explores the daily lives, particularly discretionary time, of adolescents with an autism spectrum disorder (ASD). We describe the activities and activity partners of adolescents, the factors associated with their discretionary time use, and the impact of time use on their autism symptoms. Mothers of 103 adolescents with an ASD completed two 24-hour time diaries to describe their adolescent's activity participation during the third wave of a longitudinal study. Adolescents with an ASD spent considerable time in discretionary activities, with watching television and using a computer as the most frequent activities. They most frequently spent discretionary time alone or with their mothers. They spent little time engaged in conversations or doing activities with peers. Age, gender, the presence of intellectual disability, severity of autism symptoms and maladaptive behaviors, the number of siblings, maternal education, marital status, and family income were associated with adolescent time use. Notably, greater time spent in conversation and reading predicted future decreases in severity of social impairment. The way that adolescents with an ASD spend their free time may have implications for their development and the course of their autism symptoms.
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http://dx.doi.org/10.1177/1362361310386503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572828PMC
September 2011

Siblings of individuals with an autism spectrum disorder: sibling relationships and wellbeing in adolescence and adulthood.

Autism 2009 Jan;13(1):59-80

Department of Occupational Therapy, Boston University, Boston, MA 02215, USA.

We investigated sibling relationships and wellbeing in adolescents and adults with a sibling with an autism spectrum disorder (ASD). Adolescents engaged in more shared activities than did adults. Adolescents reported greater social support, greater use of emotion-focused coping strategies, and less use of problem-focused coping than adults. In adulthood, females with a sister with ASD reported the most positive affect in the sibling relationship and men with a sister with ASD the least. Adolescents engaged in more shared activities and reported more positive affect in their sibling relationship when their sibling with ASD had fewer behavior problems; greater use of problem-focused coping buffered the negative effects of behavior problems on sibling engagement. For adults, more shared activities were observed when the sibling with ASD was younger in age and had fewer behavior problems; greater positive affect in sibling relationships was predicted by greater parental support.
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http://dx.doi.org/10.1177/1362361308097119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651641PMC
January 2009
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