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Hang Lin,1,2 Cui Zhou,1 Kai-Hang Yu,3 Yi-Shuai Lin,1 Ling-Bo Wang,1 Ying Zhang,1 Shi-Xing Liu,1 Wen-Ya Xu,1 Yao Sun,1 Tie-Li Zhou,1 Jian-Ming Cao,4 Jian-Zhong Ye1 1Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenhzou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 3Pathology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tie-Li Zhou; Jian-Zhong Ye, Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, People’s Republic of China, Email wyztli@163.com; jzye89@163.comObjective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study.Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method.Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512– 1024 μg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found.Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.Keywords: Acinetobacter baumannii, multidrug-resistance, glabridin, quorum sensing

Chang-Fu Kuo,1,2,* I-Jun Chou,3,4,* Matthew J Grainge,5 Shue-Fen Luo,2 Lai-Chu See,2,6,7 Kuang-Hui Yu,2 Weiya Zhang,1 Michael Doherty,1 Ana M Valdes1 1Division or Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK; 2Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK; 4Division of Paediatric Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; 6Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan; 7Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Purpose: To estimate the extent of familial aggregation of type 1 diabetes (T1D) and coaggregation of related chronic diseases and assess the relative contribution of environmental and genetic factors on the risks.Patients and methods: This population-based study used the Taiwan National Health Insurance database to reconstruct family structure and identify people with T1D and other chronic diseases between 1999 and 2015. Relative risks (RRs) for T1D and other chronic diseases and heritability of T1D were estimated. Heritability was estimated using the polygenic liability model.Results: Validation of family structure found the positive predictive value to be 98.7% for maternal links and 98.6% for paternal links. Having an affected twin, first-degree relative, or spouse was associated with an adjusted RR (95% CI) of 553.66 (427.59–716.89), 32.49 (28.66–36.84), and 2.17 (0.31–15.40) for T1D, respectively. Based on the polygenic liability model, heritability, shared and non-shared contributions to T1D, and variances were 66.50%, 10.86%, and 22.64%, respectively. A family history of T1D was associated with an RR (95% CI) of 1.51 (1.20–1.89) for rheumatoid arthritis, 1.66 (1.21–2.26) for Sjögren’s syndrome, 1.48 (1.09–2.01) for systemic lupus erythematosus, 1.24 (1.14–1.35) for simple goiter, 1.16 (1.04–1.31) for non-toxic nodular goiter, 1.61 (1.49–1.74) for thyrotoxicosis, 1.78 (1.57–2.01) for acquired hypothyroidism, 1.66 (1.40–1.98) for thyroiditis, and 1.15 (0.97–1.37) for epilepsy.Conclusion: These data highlight the importance of the genetic contribution to T1D and confirm the coaggregation of autoimmune and metabolic diseases with T1D. Keywords: type 1 diabetes mellitus, familial aggregation, co-aggregation, autoimmune diseases, endocrine diseases

Wen-Hsuan Tsai,1 Kun-Hua Yu,1 Yi-Cheng Huang,2 Cheng-I Lee1 1Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan, Republic of China; 2Department of Food Science, National Taiwan Ocean University, Keelung City, Taiwan, Republic of China Background: Photodynamic therapy (PDT) is an effective therapy for cancers and is a minimally invasive therapy with low dark toxicity and limited side effects. PDT employs the combination of photosensitizers with a specific light source to produce reactive oxygen species (ROS) to damage tumor cells. Methods: We fabricated nanoparticles encapsulating curcumin through crosslinking chitosan and tripolyphosphate (TPP). Additionally, the chitosan was conjugated to epidermal growth factor in order to target the epidermal growth factor receptor (EGFR), overexpressed on cancer cells. To investigate PDT using fabricated nanoparticles, we measured cell viabilities and ROS production in relation to EGFR-overexpressing gastric cancer cells and non-cancer gastric cells.Results: The targeting nanoparticles displayed a superior PDT effect in the cancer cell, with a resultant approximately fourfold decrease in the IC50. The PDT mechanism of curcumin-encapsulated nanoparticles is further identified as the generation of 1O2, the major pathway in PDT.Conclusion: These curcumin-encapsulated chitosan/TPP nanoparticles are a promising targeted-PDT against EGFR-overexpressing cancers. Keywords: EGFR-targeting, cancer, photodynamic therapy, curcumin, chitosan

AlMgB14 and AlMgB14–50 wt % TiB2 coatings deposited onto a VK-8 hard-alloy substrate by ion-plasma sputtering using powder ceramic targets are studied. It is established that the formed coatings are characterized by an amorphous-crystalline structure containing B–B, B–O, and Ti–O interatomic bonds. The composition of the target has a minor effect on the morphology and roughness of the obtained coatings. The hardness of TiB2-free coatings reaches 35 ± 2 GPa at the lowest friction coefficient of 0.12. It is established that the coatings formed using the AlMgB14–50 wt % TiB2 target possess higher adhesion strength and wear resistance. [ABSTRACT FROM AUTHOR]

Abstract Background Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. Methods We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. Results The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p