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1. Honokiol Exhibits Anti-NLRP3 Inflammasome and Antimicrobial Properties in Neisseria gonorrhoeae-Infected Macrophages

Author

Hua KF, Hsu HT, Huang MS, Chiu HW, Wong WT, Peng CH, Lin YB, Chen A, Wang CC, Hsu CH, Wu CH, Lin WY, Ho CL, and Li LH

Subjects
neisseria gonorrhoeae, honokiol, nlrp3 inflammasome, mitochondria, bactericiide, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Kuo-Feng Hua,1,2,* Hsien-Ta Hsu,3,4,* May-Shu Huang,5,6 Hsiao-Wen Chiu,1 Wei-Ting Wong,1 Chien-Hsiu Peng,1 Yu-Bei Lin,1 Ann Chen,7 Chien-Chun Wang,8,9 Chung-Hua Hsu,10,11 Chun-Hsien Wu,12 Wen-Yu Lin,1,12 Chen-Lung Ho,13 Lan-Hui Li14 1Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 3Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; 5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan; 8Infectious Disease Division, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 9Kunming Prevention and Control Center, Taipei City Hospital, Taipei, Taiwan; 10Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 11Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 12Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 13Division of Wood Cellulose, Taiwan Forestry Research Institute, Taipei, Taiwan; 14Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Lan-Hui Li, Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100, Kunming Street, Wanhua District, Taipei City, 108203, Taiwan, Tel +886-2-23703739 # 1438, Fax +886-2-23885259, Email A1525@tpech.gov.twPurpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1β, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages.Methods: Honokiol’s impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay.Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1β, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae.Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.Keywords: Neisseria gonorrhoeae, honokiol, NLRP3 inflammasome, mitochondria, bactericiide

Published
2024

2. Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study

Author

Guo H, Li LH, Lv XH, Su FZ, Chen J, Xiao F, Shi M, and Xie YB

Subjects
sleep disturbances, postoperative delirium, postoperative sleep quality, postoperative pain, anesthesia, Psychiatry, RC435-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Hao Guo,1,* Li-Heng Li,2,* Xiao-Hong Lv,1,* Feng-Zhi Su,1,* Jie Chen,1,* Fei Xiao,1,3 Min Shi,1 Yu-Bo Xie1,3 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The Guilin Municipal Hospital of Traditional Chinese Medicine, Guangxi, People’s Republic of China; 3Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Bo Xie, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530000, People’s Republic of China, Tel +86 13977121557, Email xybdoctor@163.comPurpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery.Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥ 6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD.Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04– 1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09– 9.52], P=0.034) were independent risk factors for the development of POD.Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.Keywords: sleep disturbances, postoperative delirium, postoperative sleep quality, postoperative pain, anesthesia

Published
2024

3. Leptin Induces MMP-1 Expression Through the RhoA/ERK1/2/NF-κB Axis in Human Intervertebral Disc Cartilage Endplate-Derived Stem Cells

Author

Hua KF, Li LH, Yu HC, Wong WT, and Hsu HT

Subjects
intervertebral disc degeneration, leptin, matrix metalloproteinase, intervertebral disc cartilage endplate-derived stem cells, rhoa, erk1/2, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Kuo-Feng Hua,1,2,* Lan-Hui Li,3,* Hsin-Chiao Yu,4 Wei-Ting Wong,1 Hsien-Ta Hsu4,5 1Department of Biotechnology and Animal Science, National Ilan University, Yilan, 26047, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404333, Taiwan; 3Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, 108, Taiwan; 4Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, 231, Taiwan; 5School of Medicine, Buddhist Tzu Chi University, Hualien, 970, Taiwan*These authors contributed equally to this workCorrespondence: Hsien-Ta Hsu, Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian Dist, New Taipei City, 231016, Taiwan, Tel +866-2-6628-9779, Email j1208192@ms45.hinet.netPurpose: Intervertebral disc (IVD) degeneration, associated with aging, may cause low back pain and disability, with obesity as a significant risk factor. In a prior study, we found a positive correlation between IVD degeneration and levels of matrix metalloproteinase-1 (MMP-1) and leptin. Yet, the interaction between MMP-1 and leptin in IVD degeneration is unclear. Our research seeks to explore leptin’s influence on MMP-1 expression and the underlying mechanisms in human intervertebral disc cartilage endplate-derived stem cells, specifically SV40 cells.Methods: The mRNA and protein expression in leptin-stimulated SV40 cells were assessed using RT-real-time PCR and Western blotting or ELISA, respectively. We examined leptin-mediated RhoA activation through a GTP-bound RhoA pull-down assay. Furthermore, the phosphorylation levels of mitogen-activated protein kinases and AKT in leptin-stimulated SV40 cells were analyzed using Western blotting. The activation of NF-κB by leptin was investigated by assessing phosphorylation of IKKα/β, IκBα, and NF-κB p65, along with the nuclear translocation of NF-κB p65. To understand the underlying mechanism behind leptin-mediated MMP-1 expression, we employed specific inhibitors.Results: Leptin triggered the mRNA and protein expression of MMP-1 in SV40 cells. In-depth mechanistic investigations uncovered that leptin heightened RhoA activity, promoted ERK1/2 phosphorylation, and increased NF-κB activity. However, leptin did not induce phosphorylation of JNK1/2, p38, or AKT. When we inhibited RhoA, ERK1/2, and NF-κB, it resulted in a decrease in MMP-1 expression. Conversely, inhibition of reactive oxygen species and NADPH oxidase did not yield the same outcome. Additionally, inhibiting RhoA or ERK1/2 led to a reduction in leptin-induced NF-κB activation. Moreover, inhibiting RhoA also decreased leptin-mediated ERK1/2 phosphorylation.Conclusion: These results indicated that leptin induced MMP-1 expression in SV40 cells through the RhoA/ERK1/2/NF-κB axis. This study provided the pathogenic role of leptin and suggested the potential therapeutic target for IVD degeneration. Keywords: intervertebral disc degeneration, leptin, matrix metalloproteinase, intervertebral disc cartilage endplate-derived stem cells, RhoA, ERK1/2

Published
2023

4. Antrodia cinnamomea May Interfere with the Interaction Between ACE2 and SARS-CoV-2 Spike Protein in vitro and Reduces Lung Inflammation in a Hamster Model of COVID-19

Author

Li LH, Chiu HW, Wong WT, Huang KC, Lin TW, Chen ST, and Hua KF

Subjects
coronavirus disease 2019, angiotensin-converting enzyme-2, severe acute respiratory syndrome coronavirus 2, antrodia cinnamomea, the intracellular sensor nacht, lrr, and pyd domain-containing protein 3 inflammasome, cytokine., Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Lan-Hui Li,1 Hsiao-Wen Chiu,2 Wei-Ting Wong,2 Ko-Chieh Huang,3 Tzu-Wen Lin,3 Shui-Tein Chen,3 Kuo-Feng Hua2,4 1Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 2Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan; 3ALPS Biotech Co. Ltd, Taipei, Taiwan; 4Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, TaiwanCorrespondence: Kuo-Feng Hua, Department of Biotechnology and Animal Science, National Ilan University, No. 1, Sec. 1, Shennong Road, Yilan, 260, Taiwan, Tel +886 3 931 7626, Fax +886 3 935 4794, Email kuofenghua@gmail.comPurpose: Coronavirus disease 2019 (COVID-19) poses a global health challenge with widespread transmission. Growing concerns about vaccine side effects, diminishing efficacy, and religious-based hesitancy highlight the need for alternative pharmacological approaches. Our study investigates the impact of the ethanol extract of Antrodia cinnamomea (AC), a native medicinal fungus from Taiwan, on COVID-19 in both in vitro and in vivo contexts.Methods: We measured the mRNA and protein levels of angiotensin-converting enzyme-2 (ACE2) in human lung cells using real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Additionally, we determined the enzymatic activity of ACE2 using the fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH. To assess the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we used SARS-CoV-2 pseudovirus infections in human embryonic kidney 293T cells expressing ACE2 to measure infection rates. Furthermore, we evaluated the in vivo efficacy of AC in mitigating COVID-19 by conducting experiments on hamsters infected with the Delta variant of SARS-CoV-2.Results: AC effectively decreased ACE2 mRNA and protein levels, a critical host receptor for the SARS-CoV-2 spike protein, in human lung cells. It also prevented the spike protein from binding to human lung cells. Dehydrosulphurenic acid, an isolate from AC, directly inhibited ACE2 protease activity with an inhibitory constant of 1.53 μM. In vitro experiments showed that both AC and dehydrosulphurenic acid significantly reduced the infection rate of SARS-CoV-2 pseudovirus. In hamsters infected with the Delta variant of SARS-CoV-2, oral administration of AC reduced body weight loss and improved lung injury. Notably, AC also inhibited IL-1β expression in both macrophages and the lung tissues of SARS-CoV-2-infected hamsters.Conclusion: AC shows potential as a nutraceutical for reducing the risk of SARS-CoV-2 infection by disrupting the interaction between ACE2 and the SARS-CoV-2 spike protein, and for preventing COVID-19-associated lung inflammation.Graphical Abstract: Keywords: coronavirus disease 2019, angiotensin-converting enzyme-2, severe acute respiratory syndrome coronavirus 2, Antrodia cinnamomea, the intracellular sensor NACHT, LRR, PYD domain-containing protein 3 inflammasome, cytokine

Published
2023

5. Management and Anticoagulation Treatment of Non-Valvular Atrial Fibrillation in Elderly Patients: The Dali Study

Author

Huang H, Hu NQ, Yang JY, Xiang YL, Zhu YZ, Du QR, Yin XY, Lv JL, and Li LH

Subjects
non-valvular atrial fibrillation, awareness rate of atrial fibrillation, anticoagulant therapy, stroke, all-cause death, Medicine (General), R5-920
Abstract

Hong Huang, Nai-Qing Hu, Jun-Yun Yang, Yu-Luan Xiang, Yuan-Zhao Zhu, Qian-Ru Du, Xue-Yan Yin, Jin-lin Lv, Li-Hua Li Department of Gerontology, The First Affiliated Hospital of Dali University, Dali, Yunnan Province, 671000, People’s Republic of ChinaCorrespondence: Li-Hua Li, Department of Gerontology, The First Affiliated Hospital of Dali University, Jiashibo Road 32, Dali, 671000, People’s Republic of China, Tel +86-872-2205663, Fax +86-872-2201096, Email lilihuayncn@163.comBackground: Non-valvular atrial fibrillation (NVAF) is associated with increased stroke in elderly populations, yet anticoagulant therapy is underutilized. We analyzed clinical characteristics and anticoagulation treatment rates of elderly NVAF patients hospitalized in Dali, China, to identify potential contributing factors.Methods: We collected data for 155 elderly patients with NVAF aged ≥ 60 years, from July 01, 2020, to December 31, 2021. We analyzed the awareness rate, clinical characteristics, and anticoagulant treatment rate of atrial fibrillation (AF), and identified factors influencing treatment. Patients were followed up one year after discharge to assess vital status, cardiovascular events, and anticoagulation therapy status.Results: Among 155 patients, 52.26% were female, and the average age was 75.77 years. The awareness rate of AF was 47.74% at admission, and only 21.94% received anticoagulant therapy. After discharge, the rate of anticoagulant therapy significantly increased to 70.97%, and 89.09% used new oral anticoagulants. Thromboembolic history and persistent AF predicted anticoagulant therapy at discharge, while male gender, previous bleeding history, and antiplatelet therapy predicted non-anticoagulant therapy. Out of 133 patients who completed a one-year follow-up, 23.31% died, 3.01% had strokes, and 3.01% experienced bleeding. Anticoagulant therapy decreased to 51.96% during the follow-up year.Conclusion: Our findings highlight the low awareness rate and anticoagulant treatment rate, and high mortality among elderly NVAF patients in Dali. The development of comprehensive intervention strategies is critical to standardize AF management and improve prognosis.Keywords: non-valvular atrial fibrillation, awareness rate of atrial fibrillation, anticoagulant therapy, stroke, all-cause death

Published
2023

6. Establishment and Clinical Application of a Method for Detecting T Lymphocyte Subsets by Cellular Immunochip Technology

Author

Chen C, Liu YM, Xuan SX, Zhou MF, Zhou P, Cheng B, Lin JD, Yin WG, and Li LH

Subjects
t lymphocyte, physical examination, cd4 / cd8, cellular immune chip, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Chen Chen,* Yan-Mei Liu,* Shu-Xia Xuan, Mei-Fang Zhou, Peng Zhou, Bin Cheng, Jin-Duan Lin, Wei-Guo Yin, Lin-Hai Li Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Guo Yin; Lin-Hai LiDepartment of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, People’s Republic of ChinaTel +86 763 311 3890Email wgy09dr_mn@163.com; lilinhai_abc@outlook.comObjective: To establish and verify the method for detecting the immune phenotype of peripheral blood T lymphocytes by cellular immune chip technology, analyze the immune status, and discuss its clinical diagnostic value of different populations in the Qingyuan area.Methods: First, a cellular immune chip was used to detect the number of T lymphocyte subsets CD3+, CD4+, CD8+, and CD4/CD8, followed by evaluating the accuracy and precision through a comparison with flow cytometry. After passing the performance verification, a large-scale detection was performed by a cellular immune chip in 8389 cases. Immunochip technology detects the expression of T lymphocyte subsets and analyzes the differences in cellular immune function among people with physical examination, inflammation, and cancer, as well as different cancer types and in genders.Results: The cell immunochip method and flow cytometry method have the same accuracy and precision in detecting specimens, and the former is fast and simple, and is suitable for clinical use; big data analysis is expected to establish a reference range for CD3+, CD4+, and CD8+ T cell counts in Qingyuan. There are statistical differences in CD3+, CD4+, CD8+ T cell counts in physical examination, inflammation and cancer populations; there are also certain differences in CD3+, CD4+, CD8+ T cell counts and CD4/CD8 ratios between different cancer types and different diseases.Conclusion: The method of cell immunochip technology to detect T lymphocyte subsets is simple and practical, with accurate results and rapid detection. It can be used for immune function monitoring and treatment prognosis evaluation of people with different diseases, and it is worthy of popularization and application in clinical practice.Keywords: T lymphocyte, physical examination, CD4/CD8, cellular immune chip

Published
2021

7. Effects of Trigger Point Dry Needling on Neuromuscular Performance and Pain of Individuals Affected by Patellofemoral Pain: A Randomized Controlled Trial

Author

Ma YT, Li LH, Han Q, Wang XL, Jia PY, Huang QM, and Zheng YJ

Subjects
patellofemoral pain syndrome, myofascial trigger points, stretching, Medicine (General), R5-920
Abstract

Yan-Tao Ma,1,2,* Li-Hui Li,2,3,* Qi Han,1 Xiao-Lei Wang,1 Pei-Yu Jia,1 Qiang-Min Huang,2 Yong-Jun Zheng1 1Department of Pain Management, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Sport Rehabilitation, School of Kinesiology, Shanghai University of Sport, Shanghai, People’s Republic of China; 3School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong-Jun Zheng; Qiang-Min Huang Email zhengyongjun1971@126.com; huaqia404@aliyun.comPurpose: To investigate the effects of trigger point dry needling (TrP-DN) on exercise-induced patellofemoral pain syndrome (PFPS).Patients and Methods: In this randomized, single-blind, parallel-group trial, 50 patients with PFPS were randomly allocated to the following two groups: the TrP-DN group (n = 25) and the Sham needling group (n = 25). Patients in both groups were asked to perform a stretching exercise of the quadriceps daily after needling. The needling group received a single session of TrP-DN to trigger points (TrPs) in the vastus medialis oblique (VMO), vastus lateralis (VL), and rectus femoris muscles (once a week for 6 weeks), and the Sham group received placebo needling. Visual analogue scale (VAS) for pain intensity and Kujala questionnaire for the functional status were assessed before treatment, 3 and 6 weeks after treatment, and at the 3-month follow-up. The ratio of the myoelectric amplitude of the vastus medialis oblique and vastus lateralis muscles (VMO/VL) was assessed before treatment and 6 weeks after treatment.Results: There was no significant difference in the general data between the two groups. The VAS scores and Kujala scores in the TrP-DN group were significantly improved and increased at the 3-week treatment visit, 6-week treatment visit, and 3-month follow-up compared to the scores before treatment; and the scores in the Sham group were only significantly improved at the 3-week treatment visit, and 6-week treatment visit. VAS scores in the TrP-DN group were significantly lower and Kujala scores were significantly higher at the 6-week treatment visit and the 3-month follow-up compared to those in the Sham group. The VMO/VL ratio in the TrP-DN group was significantly increased at the 6-week treatment visit compared to that before treatment.Conclusion: TrP-DN at the quadriceps combined with stretch can reduce the pain, and improves the clinical symptoms and function, the VMO/VL ratio, and the coordination of VMO and VL in patients with PFPS.Keywords: patellofemoral pain syndrome, myofascial trigger points, stretching

Published
2020

8. A sample model established by S-index predicting overall survival after curative resection of primary hepatocellular carcinoma

Author

Chen L, Cai BB, Zhou CJ, Hou XQ, Hu SP, Fang G, Chen WC, Li LH, and Yang WJ

Subjects
Primary hepatocellular carcinoma (PHCC), S-index, Nomogram, Curative resection, Prognosis., Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Lei Chen,1 Bin-Bin Cai,1 Chao-Jun Zhou,1 Xiang-Qing Hou,2 Si-Pin Hu,1 Guan Fang,3 Wen-Chao Chen,1 Lin-Hui Li,1 Wen-Jun Yang1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, Wenzhou, China; 2Department of Statistics, School of Public Health and Management, Wenzhou Medical University, Zhejiang, Wenzhou, China; 3Department of Colorectal Anus Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, Wenzhou, China Purpose: Prognostic prediction after curative resection of primary hepatocellular carcinoma (PHCC) remains an arduous task. The S-index calculated from γ-glutamyl transpeptidase, albumin, and platelets is reported to predict the severity of liver fibrosis. We constructed a nomogram for predicting the survival probability of PHCC based on a new indicator, the S-index, combined with other routine clinical parameters. Patients and methods: We selected 490 patients with PHCC postradical surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2007 and January 2014. The subjects were randomly allocated into the training cohort and the validation cohort in the ratio 7:3 by the digital method. Important variables screened by univariate analysis were included in multivariate analysis to obtain independent risk factors for predicting the prognosis of PHCC. The construction of the nomogram was based on Cox proportional hazard regression models. The concordance index (C-index) was used in the nomogram for evaluating the model performance for prognosis. We drew time-dependent receiver operating characteristic curves to compare our model with other staging systems. Results: The nomogram based on six independent risk factors after multivariate analyses had good predictive power after radical surgery of PHCC. In the training and validation groups, the C-index of the nomogram was highly consistent for evaluating survival from PHCC. Compared with the traditional scoring system, the areas under time-dependent receiver operating characteristic curves were 0.7382, 0.7293, and 0.7520 for 1-, 3-, and 5-year overall survival, respectively. In summary, the nomogram showed excellent results in terms of prognosis of PHCC. Conclusion: Based on the S-index and the other clinical indicators, we developed a precise nomogram that predicts the survival probability of patients with PHCC after radical surgery. This tool can provide effective information for surgeons and patients. Keywords: PHCC, radical resection, nomogram, prognosis

Published
2019

9. Safety and efficacy of paliperidone palmitate 1-month formulation in Chinese patients with schizophrenia: a 25-week, open-label, multicenter, Phase IV study

Author

Zhao JP, Li LH, Shi JG, Li Y, Xu XF, Li KQ, Zhang LL, Cai SL, Feng Y, Zhuo JM, Liu WH, and Lu HF

Subjects
Chinese, long-acting injectables, open-label, paliperidone palmitate, PANSS, schizophrenia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).Results: Of the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P

Published
2017

10. Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population

Author

Xie WW, Zhang L, Wu RR, Yu Y, Zhao JP, and Li LH

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Wei-Wei Xie,1,2* Lin Zhang,1* Ren-Rong Wu,1 Yan Yu,3 Jing-Ping Zhao,1 Le-Hua Li1 1Mental Health Institute of the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, 3People’s Hospital of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Background: Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood–brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a local Chinese Han population.Methods: Two hundred and ninety-two MDD patients and 208 unrelated individuals were matched by age and sex and examined using a case-control design. Six single nucleotide polymorphisms (SNPs) of the ABCB1 gene, including rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, and rs2235015, were genotyped by ligase detection reaction and multiplex polymerase chain reaction. Linkage disequilibrium and haplotype analysis were investigated in the two study groups. Results: Significant protection for MDD individuals carrying the TG haplotype of rs1045642–rs2032582 was observed (odds ratio 0.470, 95% confidence interval 0.251–0.897, P=0.01).The rs2032582 (G2677T) and rs1128503 (C1236T) SNPs of ABCB1 showed nominal associations with MDD; the other four SNPs of the ABCB1 gene were not associated with MDD.Conclusion: Chinese individuals carrying the TG haplotype of rs1045642–rs2032582 had a nearly 53% lower risk of developing MDD. To the best of our knowledge, this is the first report to analyze the effect of ABCB1 polymorphism on the risk of MDD in a Chinese population. Keywords: major depressive disorder,ABCB1 gene, single nucleotide polymorphism, pharmacogenetics

Published
2015

11. Efficacy and safety of intravenous nimodipine administration for treatment of hypertension in patients with intracerebral hemorrhage

Author

Li YQ, Fang W, Tao L, Li M, Yang YL, Gao YF, Ge SN, Gao L, Zhang B, Li ZH, Zhou W, Wang BL, and Li LH

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Yuqian Li,1,* Wei Fang,1,* Lei Tao,2,* Min Li,1 Yanlong Yang,1 Yafei Gao,1 Shunnan Ge,1 Li Gao,1 Bin Zhang,1 Zhihong Li,1 Wei Zhou,1 Boliang Wang,3 Lihong Li11Department of Neurosurgery, 2Department of Anesthesiology, 3Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this studyBackground: Nicardipine (NC) is the most commonly used antihypertensive drug in neurological patients with hypertension. Although nimodipine (NM) is widely used to treat cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage, trials exploring its antihypertensive effect after intravenous administration in subjects with intracerebral hemorrhage (ICH) are scarce.Methods: A retrospective study was carried out to compare the safety and efficacy of NC and NM administered intravenously in patients with ICH. Therapeutic responses were assessed by achievement of goal blood pressure (BP); use of additional medications for BP control; proportion of time spent within goal; variability in BP; time to goal BP; number of dose adjustments; variability in ICH volume, Glasgow Coma Scale score, and intracranial pressure; and drug-related complications.Results: A total of 87 patients were eligible for analysis (n=46 [NC]; n=41 [NM]), and baseline characteristics between groups were similar. Both agents were effective in achieving goal BP during infusion, with 93.5% and 87.8% patients in the NC and NM groups achieving goal, respectively. Fewer additional medications were needed to control BP in the NC group. BP variability was similar and no differences were observed in the mean time to goal BP and mean numbers of dose adjustments between both groups. Interestingly, intracranial pressure declined (P=0.048) during NC administration but increased (P=0.066) after NM treatment. Finally, the incidences of hematoma expansion, neurological deterioration, and adverse drug events were similar in both groups.Conclusion: NM is effective and safe for BP control in patients with ICH.Keywords: nicardipine, blood pressure, intravenous infusion

Published
2015

12. 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

Author

Kuhn, J, Adkins, S, Agwanda, B, Al Kubrusli, R, Alkhovsky, S, Amarasinghe, G, Avsic-Zupanc, T, Ayllon, M, Bahl, J, Balkema-Buschmann, A, Ballinger, M, Basler, C, Bavari, S, Beer, M, Bejerman, N, Bennett, A, Bente, D, Bergeron, E, Bird, B, Blair, C, Blasdell, K, Blystad, D, Bojko, J, Borth, W, Bradfute, S, Breyta, R, Briese, T, Brown, P, Brown, J, Buchholz, U, Buchmeier, M, Bukreyev, A, Burt, F, Buttner, C, Calisher, C, Cao, M, Casas, I, Chandran, K, Charrel, R, Cheng, Q, Chiaki, Y, Chiapello, M, Choi, I, Ciuffo, M, Clegg, J, Crozier, I, Dal Bo, E, de la Torre, J, de Lamballerie, X, de Swart, R, Debat, H, Dheilly, N, Di Cicco, E, Di Paola, N, Di Serio, F, Dietzgen, R, Digiaro, M, Dolnik, O, Drebot, M, Drexler, J, Dundon, W, Duprex, W, Durrwald, R, Dye, J, Easton, A, Ebihara, H, Elbeaino, T, Ergunay, K, Ferguson, H, Fooks, A, Forgia, M, Formenty, P, Franova, J, Freitas-Astua, J, Fu, J, Furl, S, Gago-Zachert, S, Gao, G, Garcia, M, Garcia-Sastre, A, Garrison, A, Gaskin, T, Gonzalez, J, Griffiths, A, Goldberg, T, Groschup, M, Gunther, S, Hall, R, Hammond, J, Han, T, Hepojoki, J, Hewson, R, Hong, J, Hong, N, Hongo, S, Horie, M, Hu, J, Hu, T, Hughes, H, Huttner, F, Hyndman, T, Ilyas, M, Jalkanen, R, Jiang, D, Jonson, G, Junglen, S, Kadono, F, Kaukinen, K, Kawate, M, Klempa, B, Klingstrom, J, Kobinger, G, Koloniuk, I, Kondo, H, Koonin, E, Krupovic, M, Kubota, K, Kurath, G, Laenen, L, Lambert, A, Langevin, S, Lee, B, Lefkowitz, E, Leroy, E, Li, S, Li, L, Li, J, Liu, H, Lukashevich, I, Maes, P, de Souza, W, Marklewitz, M, Marshall, S, Marzano, S, Massart, S, Mccauley, J, Melzer, M, Mielke-Ehret, N, Miller, K, Ming, T, Mirazimi, A, Mordecai, G, Muhlbach, H, Muhlberger, E, Naidu, R, Natsuaki, T, Navarro, J, Netesov, S, Neumann, G, Nowotny, N, Nunes, M, Olmedo-Velarde, A, Palacios, G, Pallas, V, Palyi, B, Papa, A, Paraskevopoulou, S, Park, A, Parrish, C, Patterson, D, Pauvolid-Correa, A, Paweska, J, Payne, S, Peracchio, C, Perez, D, Postler, T, Qi, L, Radoshitzky, S, Resende, R, Reyes, C, Rima, B, Luna, G, Romanowski, V, Rota, P, Rubbenstroth, D, Rubino, L, Runstadler, J, Sabanadzovic, S, Sall, A, Salvato, M, Sang, R, Sasaya, T, Schulze, A, Schwemmle, M, Shi, M, Shi, X, Shi, Z, Shimomoto, Y, Shirako, Y, Siddell, S, Simmonds, P, Sironi, M, Smagghe, G, Smither, S, Song, J, Spann, K, Spengler, J, Stenglein, M, Stone, D, Sugano, J, Suttle, C, Tabata, A, Takada, A, Takeuchi, S, Tchouassi, D, Teffer, A, Tesh, R, Thornburg, N, Tomitaka, Y, Tomonaga, K, Tordo, N, Torto, B, Towner, J, Tsuda, S, Tu, C, Turina, M, Tzanetakis, I, Uchida, J, Usugi, T, Vaira, A, Vallino, M, van den Hoogen, B, Varsani, A, Vasilakis, N, Verbeek, M, von Bargen, S, Wada, J, Wahl, V, Walker, P, Wang, L, Wang, G, Wang, Y, Waqas, M, Wei, T, Wen, S, Whitfield, A, Williams, J, Wolf, Y, Wu, J, Xu, L, Yanagisawa, H, Yang, C, Yang, Z, Zerbini, F, Zhai, L, Zhang, Y, Zhang, S, Zhang, J, Zhang, Z, Zhou, X, Kuhn JH, Adkins S, Agwanda BR, Al Kubrusli R, Alkhovsky SV, Amarasinghe GK, Avsic-Zupanc T, Ayllon MA, Bahl J, Balkema-Buschmann A, Ballinger MJ, Basler CF, Bavari S, Beer M, Bejerman N, Bennett AJ, Bente DA, Bergeron E, Bird BH, Blair CD, Blasdell KR, Blystad DR, Bojko J, Borth WB, Bradfute S, Breyta R, Briese T, Brown PA, Brown JK, Buchholz UJ, Buchmeier MJ, Bukreyev A, Burt F, Buttner C, Calisher CH, Cao MJ, Casas I, Chandran K, Charrel RN, Cheng Q, Chiaki Y, Chiapello M, Choi I, Ciuffo M, Clegg JCS, Crozier I, Dal Bo E, de la Torre JC, de Lamballerie X, de Swart RL, Debat H, Dheilly NM, Di Cicco E, Di Paola N, Di Serio F, Dietzgen RG, Digiaro M, Dolnik O, Drebot MA, Drexler JF, Dundon WG, Duprex WP, Durrwald R, Dye JM, Easton AJ, Ebihara H, Elbeaino T, Ergunay K, Ferguson HW, Fooks AR, Forgia M, Formenty PBH, Franova J, Freitas-Astua J, Fu JJ, Furl S, Gago-Zachert S, Gao GF, Garcia ML, Garcia-Sastre A, Garrison AR, Gaskin T, Gonzalez JPJ, Griffiths A, Goldberg TL, Groschup MH, Gunther S, Hall RA, Hammond J, Han T, Hepojoki J, Hewson R, Hong J, Hong N, Hongo S, Horie M, Hu JS, Hu T, Hughes HR, Huttner F, Hyndman TH, Ilyas M, Jalkanen R, Jiang DH, Jonson GB, Junglen S, Kadono F, Kaukinen KH, Kawate M, Klempa B, Klingstrom J, Kobinger G, Koloniuk I, Kondo H, Koonin EV, Krupovic M, Kubota K, Kurath G, Laenen L, Lambert AJ, Langevin SL, Lee B, Lefkowitz EJ, Leroy EM, Li SR, Li LH, Li JR, Liu HZ, Lukashevich IS, Maes P, de Souza WM, Marklewitz M, Marshall SH, Marzano SYL, Massart S, McCauley JW, Melzer M, Mielke-Ehret N, Miller KM, Ming TJ, Mirazimi A, Mordecai GJ, Muhlbach HP, Muhlberger E, Naidu R, Natsuaki T, Navarro JA, Netesov SV, Neumann G, Nowotny N, Nunes MRT, Olmedo-Velarde A, Palacios G, Pallas V, Palyi B, Papa A, Paraskevopoulou S, Park AC, Parrish CR, Patterson DA, Pauvolid-Correa A, Paweska JT, Payne S, Peracchio C, Perez DR, Postler TS, Qi LY, Radoshitzky SR, Resende RO, Reyes CA, Rima BK, Luna GR, Romanowski V, Rota P, Rubbenstroth D, Rubino L, Runstadler JA, Sabanadzovic S, Sall AA, Salvato MS, Sang RS, Sasaya T, Schulze AD, Schwemmle M, Shi M, Shi XH, Shi ZL, Shimomoto Y, Shirako Y, Siddell SG, Simmonds P, Sironi M, Smagghe G, Smither S, Song JW, Spann K, Spengler JR, Stenglein MD, Stone DM, Sugano J, Suttle CA, Tabata A, Takada A, Takeuchi S, Tchouassi DP, Teffer A, Tesh RB, Thornburg NJ, Tomitaka Y, Tomonaga K, Tordo N, Torto B, Towner JS, Tsuda S, Tu CC, Turina M, Tzanetakis IE, Uchida J, Usugi T, Vaira AM, Vallino M, van den Hoogen B, Varsani A, Vasilakis N, Verbeek M, von Bargen S, Wada J, Wahl V, Walker PJ, Wang LF, Wang GP, Wang YX, Wang YQ, Waqas M, Wei TY, Wen SH, Whitfield AE, Williams JV, Wolf YI, Wu JX, Xu L, Yanagisawa H, Yang CX, Yang ZK, Zerbini FM, Zhai L, Zhang YZ, Zhang S, Zhang JG, Zhang Z, Zhou XP, Kuhn, J, Adkins, S, Agwanda, B, Al Kubrusli, R, Alkhovsky, S, Amarasinghe, G, Avsic-Zupanc, T, Ayllon, M, Bahl, J, Balkema-Buschmann, A, Ballinger, M, Basler, C, Bavari, S, Beer, M, Bejerman, N, Bennett, A, Bente, D, Bergeron, E, Bird, B, Blair, C, Blasdell, K, Blystad, D, Bojko, J, Borth, W, Bradfute, S, Breyta, R, Briese, T, Brown, P, Brown, J, Buchholz, U, Buchmeier, M, Bukreyev, A, Burt, F, Buttner, C, Calisher, C, Cao, M, Casas, I, Chandran, K, Charrel, R, Cheng, Q, Chiaki, Y, Chiapello, M, Choi, I, Ciuffo, M, Clegg, J, Crozier, I, Dal Bo, E, de la Torre, J, de Lamballerie, X, de Swart, R, Debat, H, Dheilly, N, Di Cicco, E, Di Paola, N, Di Serio, F, Dietzgen, R, Digiaro, M, Dolnik, O, Drebot, M, Drexler, J, Dundon, W, Duprex, W, Durrwald, R, Dye, J, Easton, A, Ebihara, H, Elbeaino, T, Ergunay, K, Ferguson, H, Fooks, A, Forgia, M, Formenty, P, Franova, J, Freitas-Astua, J, Fu, J, Furl, S, Gago-Zachert, S, Gao, G, Garcia, M, Garcia-Sastre, A, Garrison, A, Gaskin, T, Gonzalez, J, Griffiths, A, Goldberg, T, Groschup, M, Gunther, S, Hall, R, Hammond, J, Han, T, Hepojoki, J, Hewson, R, Hong, J, Hong, N, Hongo, S, Horie, M, Hu, J, Hu, T, Hughes, H, Huttner, F, Hyndman, T, Ilyas, M, Jalkanen, R, Jiang, D, Jonson, G, Junglen, S, Kadono, F, Kaukinen, K, Kawate, M, Klempa, B, Klingstrom, J, Kobinger, G, Koloniuk, I, Kondo, H, Koonin, E, Krupovic, M, Kubota, K, Kurath, G, Laenen, L, Lambert, A, Langevin, S, Lee, B, Lefkowitz, E, Leroy, E, Li, S, Li, L, Li, J, Liu, H, Lukashevich, I, Maes, P, de Souza, W, Marklewitz, M, Marshall, S, Marzano, S, Massart, S, Mccauley, J, Melzer, M, Mielke-Ehret, N, Miller, K, Ming, T, Mirazimi, A, Mordecai, G, Muhlbach, H, Muhlberger, E, Naidu, R, Natsuaki, T, Navarro, J, Netesov, S, Neumann, G, Nowotny, N, Nunes, M, Olmedo-Velarde, A, Palacios, G, Pallas, V, Palyi, B, Papa, A, Paraskevopoulou, S, Park, A, Parrish, C, Patterson, D, Pauvolid-Correa, A, Paweska, J, Payne, S, Peracchio, C, Perez, D, Postler, T, Qi, L, Radoshitzky, S, Resende, R, Reyes, C, Rima, B, Luna, G, Romanowski, V, Rota, P, Rubbenstroth, D, Rubino, L, Runstadler, J, Sabanadzovic, S, Sall, A, Salvato, M, Sang, R, Sasaya, T, Schulze, A, Schwemmle, M, Shi, M, Shi, X, Shi, Z, Shimomoto, Y, Shirako, Y, Siddell, S, Simmonds, P, Sironi, M, Smagghe, G, Smither, S, Song, J, Spann, K, Spengler, J, Stenglein, M, Stone, D, Sugano, J, Suttle, C, Tabata, A, Takada, A, Takeuchi, S, Tchouassi, D, Teffer, A, Tesh, R, Thornburg, N, Tomitaka, Y, Tomonaga, K, Tordo, N, Torto, B, Towner, J, Tsuda, S, Tu, C, Turina, M, Tzanetakis, I, Uchida, J, Usugi, T, Vaira, A, Vallino, M, van den Hoogen, B, Varsani, A, Vasilakis, N, Verbeek, M, von Bargen, S, Wada, J, Wahl, V, Walker, P, Wang, L, Wang, G, Wang, Y, Waqas, M, Wei, T, Wen, S, Whitfield, A, Williams, J, Wolf, Y, Wu, J, Xu, L, Yanagisawa, H, Yang, C, Yang, Z, Zerbini, F, Zhai, L, Zhang, Y, Zhang, S, Zhang, J, Zhang, Z, Zhou, X, Kuhn JH, Adkins S, Agwanda BR, Al Kubrusli R, Alkhovsky SV, Amarasinghe GK, Avsic-Zupanc T, Ayllon MA, Bahl J, Balkema-Buschmann A, Ballinger MJ, Basler CF, Bavari S, Beer M, Bejerman N, Bennett AJ, Bente DA, Bergeron E, Bird BH, Blair CD, Blasdell KR, Blystad DR, Bojko J, Borth WB, Bradfute S, Breyta R, Briese T, Brown PA, Brown JK, Buchholz UJ, Buchmeier MJ, Bukreyev A, Burt F, Buttner C, Calisher CH, Cao MJ, Casas I, Chandran K, Charrel RN, Cheng Q, Chiaki Y, Chiapello M, Choi I, Ciuffo M, Clegg JCS, Crozier I, Dal Bo E, de la Torre JC, de Lamballerie X, de Swart RL, Debat H, Dheilly NM, Di Cicco E, Di Paola N, Di Serio F, Dietzgen RG, Digiaro M, Dolnik O, Drebot MA, Drexler JF, Dundon WG, Duprex WP, Durrwald R, Dye JM, Easton AJ, Ebihara H, Elbeaino T, Ergunay K, Ferguson HW, Fooks AR, Forgia M, Formenty PBH, Franova J, Freitas-Astua J, Fu JJ, Furl S, Gago-Zachert S, Gao GF, Garcia ML, Garcia-Sastre A, Garrison AR, Gaskin T, Gonzalez JPJ, Griffiths A, Goldberg TL, Groschup MH, Gunther S, Hall RA, Hammond J, Han T, Hepojoki J, Hewson R, Hong J, Hong N, Hongo S, Horie M, Hu JS, Hu T, Hughes HR, Huttner F, Hyndman TH, Ilyas M, Jalkanen R, Jiang DH, Jonson GB, Junglen S, Kadono F, Kaukinen KH, Kawate M, Klempa B, Klingstrom J, Kobinger G, Koloniuk I, Kondo H, Koonin EV, Krupovic M, Kubota K, Kurath G, Laenen L, Lambert AJ, Langevin SL, Lee B, Lefkowitz EJ, Leroy EM, Li SR, Li LH, Li JR, Liu HZ, Lukashevich IS, Maes P, de Souza WM, Marklewitz M, Marshall SH, Marzano SYL, Massart S, McCauley JW, Melzer M, Mielke-Ehret N, Miller KM, Ming TJ, Mirazimi A, Mordecai GJ, Muhlbach HP, Muhlberger E, Naidu R, Natsuaki T, Navarro JA, Netesov SV, Neumann G, Nowotny N, Nunes MRT, Olmedo-Velarde A, Palacios G, Pallas V, Palyi B, Papa A, Paraskevopoulou S, Park AC, Parrish CR, Patterson DA, Pauvolid-Correa A, Paweska JT, Payne S, Peracchio C, Perez DR, Postler TS, Qi LY, Radoshitzky SR, Resende RO, Reyes CA, Rima BK, Luna GR, Romanowski V, Rota P, Rubbenstroth D, Rubino L, Runstadler JA, Sabanadzovic S, Sall AA, Salvato MS, Sang RS, Sasaya T, Schulze AD, Schwemmle M, Shi M, Shi XH, Shi ZL, Shimomoto Y, Shirako Y, Siddell SG, Simmonds P, Sironi M, Smagghe G, Smither S, Song JW, Spann K, Spengler JR, Stenglein MD, Stone DM, Sugano J, Suttle CA, Tabata A, Takada A, Takeuchi S, Tchouassi DP, Teffer A, Tesh RB, Thornburg NJ, Tomitaka Y, Tomonaga K, Tordo N, Torto B, Towner JS, Tsuda S, Tu CC, Turina M, Tzanetakis IE, Uchida J, Usugi T, Vaira AM, Vallino M, van den Hoogen B, Varsani A, Vasilakis N, Verbeek M, von Bargen S, Wada J, Wahl V, Walker PJ, Wang LF, Wang GP, Wang YX, Wang YQ, Waqas M, Wei TY, Wen SH, Whitfield AE, Williams JV, Wolf YI, Wu JX, Xu L, Yanagisawa H, Yang CX, Yang ZK, Zerbini FM, Zhai L, Zhang YZ, Zhang S, Zhang JG, Zhang Z, and Zhou XP

Abstract

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Published
2021

13. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate

Author

Sanchez-Felipe, L, Vercruysse, T, Sharma, S, Ma, J, Lemmens, V, Van Looveren, D, Arkalagud Javarappa, MP, Boudewijns, R, Malengier-Devlies, B, Liesenborghs, L, Kaptein, SJF, De Keyzer, C, Bervoets, L, Debaveye, S, Rasulova, M, Seldeslachts, L, Li, LH, Jansen, S, Yakass, MB, Verstrepen, BE, Böszörményi, KP, Kiemenyi-Kayere, G, van Driel, N, Quaye, O, Zhang, X, Horst, S, Mishra, N, Deboutte, W, Matthijnssens, J, Coelmont, L, Vandermeulen, C, Heylen, E, Vergote, V, Schols, D, Wang, Zhongde, Bogers, W, Kuiken, Thijs, Verschoor, E, Cawthorne, C, Van Laere, K, Opdenakker, G, Velde, G, Weynand, B, Teuwen, DE, Matthys, P, Neyts, J, Jan Thibaut, H, Dallmeier, K, Sanchez-Felipe, L, Vercruysse, T, Sharma, S, Ma, J, Lemmens, V, Van Looveren, D, Arkalagud Javarappa, MP, Boudewijns, R, Malengier-Devlies, B, Liesenborghs, L, Kaptein, SJF, De Keyzer, C, Bervoets, L, Debaveye, S, Rasulova, M, Seldeslachts, L, Li, LH, Jansen, S, Yakass, MB, Verstrepen, BE, Böszörményi, KP, Kiemenyi-Kayere, G, van Driel, N, Quaye, O, Zhang, X, Horst, S, Mishra, N, Deboutte, W, Matthijnssens, J, Coelmont, L, Vandermeulen, C, Heylen, E, Vergote, V, Schols, D, Wang, Zhongde, Bogers, W, Kuiken, Thijs, Verschoor, E, Cawthorne, C, Van Laere, K, Opdenakker, G, Velde, G, Weynand, B, Teuwen, DE, Matthys, P, Neyts, J, Jan Thibaut, H, and Dallmeier, K

Abstract

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and—concomitantly—protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

Published
2021

14. Near-Field Excited Archimedean-like Tiling Patterns in Phonon-Polaritonic Crystals.

Author

Yang, J, Krix, ZE, Kim, S, Tang, J, Mayyas, M, Wang, Y, Watanabe, K, Taniguchi, T, Li, LH, Hamilton, AR, Aharonovich, I, Sushkov, OP, Kalantar-Zadeh, K, Yang, J, Krix, ZE, Kim, S, Tang, J, Mayyas, M, Wang, Y, Watanabe, K, Taniguchi, T, Li, LH, Hamilton, AR, Aharonovich, I, Sushkov, OP, and Kalantar-Zadeh, K

Abstract

Phonon-polaritons (PhPs) arise from the strong coupling of photons to optical phonons. They offer light confinement and harnessing below the diffraction limit for applications including sensing, imaging, superlensing, and photonics-based communications. However, structures consisting of both suspended and supported hyperbolic materials on periodic dielectric substrates are yet to be explored. Here we investigate phonon-polaritonic crystals (PPCs) that incorporate hyperbolic hexagonal boron nitride (hBN) to a silicon-based photonic crystal. By using the near-field excitation in scattering-type scanning near-field optical microscopy (s-SNOM), we resolved two types of repetitive local field distribution patterns resembling the Archimedean-like tiling on hBN-based PPCs, i.e., dipolar-like field distributions and highly dispersive PhP interference patterns. We demonstrate the tunability of PPC band structures by varying the thickness of hyperbolic materials, supported by numerical simulations. Lastly, we conducted scattering-type nanoIR spectroscopy to confirm the interaction of hBN with photonic crystals. The introduced PPCs will provide the base for fabricating essential subdiffraction components of advanced optical systems in the mid-IR range.

Published
2021

17. Tunable broadband terahertz polarizer using graphene-metal hybrid metasurface

Author

Meng, K, Park, SJ, Li, LH, Bacon, DR, Chen, L, Chae, K, Park, JY, Burnett, AD, Linfield, EH, Davies, AG, and Cunningham, JE

Subjects
Physics::Optics
Abstract

We demonstrate an electrically tunable polarizer for terahertz (THz) frequency electromagnetic waves formed from a hybrid graphene-metal metasurface. Broadband (>3 THz) polarization-dependent modulation of THz transmission is demonstrated as a function of the graphene conductivity for various wire grid geometries, each tuned by gating using an overlaid ion gel. We show a strong enhancement of modulation (up to ∼17 times) compared to graphene wire grids in the frequency range of 0.2–2.5 THz upon introduction of the metallic elements. Theoretical calculations, considering both plasmonic coupling and Drude absorption, are in good agreement with our experimental findings.

Published
2019

18. Detection sensitivity of laser feedback interferometry using a terahertz quantum cascade laser

Author

Keeley, J, Bertling, K, Rubino, PL, Lim, YL, Taimre, T, Qi, X, Kundu, I, Li, LH, Indjin, D, Rakic, AD, Linfield, EH, Davies, AG, and Dean, P

Subjects
Physics::Optics, Physics::Atomic Physics
Abstract

We report on the high detection sensitivity of a laser feedback interferometry scheme based on a terahertz frequency quantum cascade laser. We show that variations on the laser voltage induced by optical feedback to the laser can be resolved with reinjection of powers as low as ~−125 dB of the emitted power. Our measurements demonstrate a noise equivalent power of ~1.4 pW/√Hz, although after accounting for reinjection losses we estimate this corresponds to only ~1 fW/√Hz being coupled to the quantum cascade laser active region.

Published
2019

19. Atomically Thin Boron Nitride as an Ideal Spacer for Metal-Enhanced Fluorescence.

Author

Gan, W, Tserkezis, C, Cai, Q, Falin, A, Mateti, S, Nguyen, M, Aharonovich, I, Watanabe, K, Taniguchi, T, Huang, F, Song, L, Kong, L, Chen, Y, Li, LH, Gan, W, Tserkezis, C, Cai, Q, Falin, A, Mateti, S, Nguyen, M, Aharonovich, I, Watanabe, K, Taniguchi, T, Huang, F, Song, L, Kong, L, Chen, Y, and Li, LH

Abstract

Metal-enhanced fluorescence (MEF) considerably enhances the luminescence for various applications, but its performance largely depends on the dielectric spacer between the fluorophore and plasmonic system. It is still challenging to produce a defect-free spacer having an optimized thickness with a sub-nanometer accuracy that enables reusability without affecting the enhancement. In this study, we demonstrate the use of atomically thin hexagonal boron nitride (BN) as an ideal MEF spacer owing to its multifold advantages over the traditional dielectric thin films. With rhodamine 6G as a representative fluorophore, it largely improves the enhancement factor (up to ∼95 ± 5), sensitivity (10-8 M), reproducibility, and reusability (∼90% of the plasmonic activity is retained after 30 cycles of heating at 350 °C in air) of MEF. This can be attributed to its two-dimensional structure, thickness control at the atomic level, defect-free quality, high affinities to aromatic fluorophores, good thermal stability, and excellent impermeability. The atomically thin BN spacers could increase the use of MEF in different fields and industries.

Published
2019

20. A high electron mobility phonotransistor

Author

Poyser, CL, Li, LH, Campion, RP, Akimov, AV, Linfield, EH, Davies, AG, Cunningham, JE, and Kent, AJ

Subjects
Computer Science::Sound, lcsh:QB460-466, lcsh:Astrophysics, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect, lcsh:Physics, lcsh:QC1-999
Abstract

Acoustoelectric devices convert acoustic energy to electrical energy and vice versa. Devices working at much higher acoustic frequencies than those currently available have potential scientific and technological applications, for example, as detectors in phononics experiments and as transducers in bulk acoustic wave filters at terahertz (THz) frequencies. Here we demonstrated an active acoustoelectronic device based on a GaAs heterostructure: an acoustically gated transistor or phonotransistor. Instead of being controlled in the conventional manner by an electrical signal applied to a metallic or semiconductor gate as in a high electron mobility transistor (HEMT), the drain-source current was controlled by a bulk sub-THz acoustic wave passing through the channel in a direction perpendicular to the current flow.

Published
2018

21. Silver-based surface plasmon waveguide for terahertz quantum cascade lasers

Author

Han, Y, Li, LH, Zhu, J, Valavanis, A, Freeman, JR, Chen, L, Rosamond, M, Dean, P, Davies, AG, Linfield, EH, and Hoffman, A

Subjects
Physics::Optics
Abstract

Terahertz-frequency quantum cascade lasers (THz QCLs) based on ridge waveguides incorporating silver waveguide layers have been investigated theoretically and experimentally, and compared with traditional gold-based devices. The threshold gain associated with silver-, gold- and copper-based devices, and the effects of titanium adhesion layers and top contact layers, in both surface-plasmon and double-metal waveguide geometries, have been analysed. Our simulations show that silver-based waveguides yield lower losses for THz QCLs across all practical operating temperatures and frequencies. Experimentally, QCLs with silver-based surface-plasmon waveguides were found to exhibit higher operating temperatures and higher output powers compared to those with identical but gold-based waveguides. Specifically, for a three-well resonant phonon active region with a scaled oscillator strength of 0.43 and doping density of 6.83 × 10¹⁵ cm‾³, an increase of 5 K in the maximum operating temperature and 40% increase in the output power were demonstrated. These effects were found to be dependent on the active region design, and greater improvements were observed for QCLs with a larger radiative diagonality. Our results indicate that silver-based waveguide structures could potentially enable THz QCLs to operate at high temperatures.

Published
2018

22. Broadband terahertz gas spectroscopy through multimode self-mixing in a quantum cascade laser

Author

Han, YJ, Partington, J, Valavanis, A, Chhantyal-Pun, R, Henry, M, Auriacombe, O, Rawlings, T, Li, LH, Keeley, J, Oldfield, M, Brewster, N, Rui, D, Dean, P, Davies, AG, Ellison, BN, and Linfield, EH

Subjects
Physics::Optics
Abstract

In the terahertz (THz) frequency range, CBRN agents and explosives have unique spectral signatures, which can be used for their identification and analysis. Quantum cascade lasers (QCLs) are important sources for spectroscopy within the 2–5 THz range, and self-mixing (SM) interference in a laser cavity enables the laser device to act both as a radiation source and as a coherent detector. This technique removes the need for additional detectors. Here, we present a SM spectroscopy technique, with an integrated frequency monitoring system and demonstrate the measurement of methanol spectral features simultaneously from two modes of a multi-mode THz QCL over a 17 GHz bandwidth.

Published
2018

23. Assessing the interactions between the associations of common genetic variants on 2q35 and 16q12 with breast cancer risk

Author

Zhu P, Yang Xd, Fan Yl, Yu B, Guo Zj, Yang Xj, and Li Lh

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Pathology, business.industry, BRCA mutation, Genome-wide association study, Odds ratio, Disease, medicine.disease, Breast cancer, Polymorphism (computer science), Internal medicine, Progesterone receptor, medicine, business, Genetic association
Abstract

UNLABELLED Genome-wide association studies (GWAS) have identified 2q35 and 16q12 as breast cancer (BC) susceptibility loci. However, the association between the two polymorphisms and BC remains controversial and inconsistent. We therefore performed a more precise estimation of these relationships by meta-analysing the currently available evidence from the literature. The PubMed, Ovid, Medline and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strengths of the associations. Thirty studies, including 106,312 cases and 140,939 controls, were identified. Overall, significantly elevated breast cancer risk was associated with the A allele of 2q35 rs13387042 when all studies were pooled into the meta-analysis (OR 1.11, 95%CI 1.07-1.15). Additionally, the T allele of 16q12 rs3803662 was associated with significantly increased breast cancer risk (OR 1.20, 95%CI 1.16-1.24). When stratifying for ethnicity, significantly increased risks were found among Caucasians, Asians and mixed ethnicities for both rs13387042 and rs3803662. For rs13387042, an association was observed for both oestrogen receptor-positive (ER+) (OR 1.14, 95%CI 1.11-1.17) and ER-negative (ER-) disease (OR 1.05, 95%CI 1.01-1.09) and for progesterone receptor-positive (PR+) (OR 1.16, 95%CI 1.12-1.19) and PR-negative (PR-) disease (OR 1.07, 95%CI 1.03-1.12). Similarly, a stronger association was observed for rs3803662 with ER+ tumors (OR 1.23, 95%CI 1.13-1.32) compared with ER- tumors (OR 1.08, 95%CI 0.97-1.20), and the same condition occurred for the polymorphism with PR+ tumors (OR 1.26, 95%CI 1.02-1.55) versus with PR- tumors (OR 1.15, 95%CI 0.90-1.46). When stratified by BRCA mutation status, a stronger association was observed with BRCA2 carriers (OR 1.23, 95%CI 1.05-1.44) than BRCA1 carriers (OR 1.09, 95%CI 1.04-1.15). In conclusion, this meta-analysis demonstrated that the A allele of 2q35 rs13387042 and the T allele of 16q12 rs3803662 are risk factors associated with increased breast cancer susceptibility. KEYWORDS rs13387042, rs3803662, oestrogen receptor, progesterone receptor, breast cancer, meta-analysis.

Published
2015

24. Synthesis of Composite Nanosheets of Graphene and Boron Nitride and Their Lubrication Application in Oil

Author

Liu, Y, Mateti, S, Li, C, Liu, X, Glushenkov, AM, Liu, D, Li, LH, Fabijanic, D, Chen, Y, Liu, Y, Mateti, S, Li, C, Liu, X, Glushenkov, AM, Liu, D, Li, LH, Fabijanic, D, and Chen, Y

Abstract

Composite nanosheets of graphene and boron nitride have been produced in large quantities for the first time using high‐energy ball milling in ammonia gas as an exfoliation agent. The anti‐wear properties of the composite nanosheets as a lubricant additive are investigated via a four‐ball method. The results show that the composite nanosheets are exfoliated from the commercial graphite and h‐BN powders and combined into graphene/BN composite nanosheets during the ball milling process. The composite nanosheets formed have diameters larger than 200 nm and consist of heterostructures of approximately 10 monolayers of graphene and BN. The composite nanosheets exhibit better wear resistance and friction reduction properties than the homogeneous nanosheets because of the stronger interaction between graphene and BN nanosheets, which can effectively improve the anti‐wear properties of mineral base oil as a lubricant additive.

Published
2018

25. Injection locking of a terahertz quantum cascade laser to a telecommunications wavelength frequency comb

Author

Freeman, JR, Ponnampalam, L, Shams, H, Mohandas, RA, Renaud, CC, Dean, P, Li, LH, Davies, AG, Seeds, AJ, and Linfield, EH

Subjects
Physics::Optics
Abstract

High resolution spectroscopy can not only identify atoms and molecules, but can also provide detailed information on their chemical and physical environment, and relative motion. In the terahertz frequency region of the electromagnetic spectrum, where many molecules have fundamental vibrational modes, there is a lack of powerful sources with narrow linewidths that can be used for absorption measurements or as local oscillators in heterodyne detectors. The most promising solid-state source is the THz frequency quantum cascade laser (QCL), however, the linewidth of this compact semiconductor laser is typically too broad for many applications and its frequency is not directly referenced to primary frequency standards. In this work we injection lock a QCL operating at 2 THz to a compact fibre-based telecommunications wavelength frequency comb, where the comb line spacing is referenced to a microwave frequency reference. This results in the QCL frequency locking to an integer harmonic of the microwave reference, and the QCL linewidth reducing to the multiplied linewidth of the microwave reference, < 100 Hz. Furthermore, we perform phase-resolved detection of the locked QCL and measure the phase noise of the locked system to be –75 dBc/Hz at 10 kHz offset from 2 THz carrier.

Published
2017

26. On-chip Terahertz-Frequency Measurements of Liquids

Author

Swithenbank, M, Burnett, AD, Russell, C, Li, LH, Davies, AG, Linfield, EH, Cunningham, JE, and Wood, CD

Abstract

Terahertz-frequency-range measurements can offer potential insight into the picosecond dynamics, and therefore function, of many chemical systems. There is a need to develop technologies capable of performing such measurements in aqueous and polar environments, particularly when it is necessary to maintain the full functionality of biological samples. In this study, we present a proof-of-concept technology comprising an on-chip planar Goubau line, integrated with a microfluidic channel, which is capable of low-loss, terahertz-frequency-range spectroscopic measurements of liquids. We also introduce a mathematical model that accounts for changes in the electric field distribution around the waveguide, allowing accurate, frequency-dependent liquid parameters to be extracted. We demonstrate the sensitivity of this technique by measuring a homologous alcohol series across the 0.1-0.8 THz frequency range.

Published
2017

27. Multi-Watt high-power THz frequency quantum cascade lasers

Author

Li, LH, Chen, L, Freeman, J, Salih, M, Dean, P, Davies, AG, and Linfield, EH

Abstract

Multi-Watt high power terahertz (THz) frequency quantum cascade lasers are demonstrated, based on a single, epitaxially-grown, 24-μm-thick active region embedded into a surface-plasmon waveguide. The devices emit in pulsed mode at a frequency of ~4.4 THz, and have a maximum operating temperature of 132 K. The maximum measurable emitted powers from a single facet are ∼2.4 W at 10 K and ∼1.8 W at 77 K, with no correction being made for the optical collection efficiency of the apparatus, or absorption by the cryostat polyethylene window.

Published
2017
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28. Patch antenna microcavity terahertz sources with enhanced emission

Author

Madéo, J, Todorov, Y, Gilman, A, Frucci, G, LI, LH, Davies, AG, Linfield, EH, Sirtori, C, and Dani, KM

Subjects
Physics::Optics
Abstract

We study the emission properties of an electroluminescent THz frequency quantum cascade structure embedded in an array of patch antenna double-metal microcavities. We show that high photon extraction efficiencies can be obtained by adjusting the active region thickness and array periodicity as well as high Purcell factors (up to 65), leading to an enhanced overall emitted power. Up to a 44-fold increase in power is experimentally observed in comparison with a reference device processed in conventional mesa geometry. Estimation of the Purcell factors using electromagnetic simulations and the theoretical extraction efficiency are in agreement with the observed power enhancement and show that, in these microcavities, the overall enhancement solely depends on the square of the total quality factor.

Published
2016

29. Spectral Characterisation of a Terahertz QCL through Self-Mixing

Author

Keeley, J, Freeman, J, Valavanis, A, Mohandas, R, Bertling, K, Taimre, T, Lim, YL, Li, LH, Indjin, D, Rakić, AD, Linfield, EH, Davies, AG, and Dean, P

Subjects
Physics::Optics
Abstract

The use of a single terahertz (THz) quantum cascade laser (QCL) device as both emitter and detector in a self-mixing (SM) scheme allows for the development of fast, sensitive and compact coherent systems for imaging and interferometry [1]. In this scheme, radiation re-injected to the laser cavity interferes (‘mixes’) with the intra-cavity electric field, causing small variations in the fundamental laser parameters, as described in the seminal paper by Lang and Kobashi (L–K) [2]. In particular, the voltage perturbation induced by optical feedback is described by a sinusoidal variation dependent on both the external cavity length LExt and the emission frequency under feedback ν, and is given byΔVsm ∝ cos(2 v/c). As such, interferometric fringes can be acquired in a SM system by simply changing the external cavity length and concurrently monitoring the terminal voltage of the device. In this work we demonstrate the use of SM interferometry for performing spectral characterisation of a multi-mode THz QCL in a scheme that offers much reduced experimental complexity when compared with typical Fourier Transform infrared spectroscopy (FTIR) systems. In addition, we report the first direct measurements of the perturbation of the lasing frequency under feedback, and compare the results with predictions from the L–K model.

Published
2016

30. Self-Mixing as a means of Spectral Characterisation of a Terahertz QCL

Author

Keeley, J, Freeman, J, Valavanis, A, Mohandas, R, Bertling, K, Taimre, T, Lim, YL, Li, LH, Indjin, D, Rakić, AD, Linfield, EH, Davies, AG, and Dean, P

Subjects
Physics::Optics
Abstract

Fast, sensitive and compact coherent systems for imaging and interferometry can be developed through the use of a single terahertz (THz) quantum cascade laser (QCL) device as both emitter and detector in a self-mixing (SM) scheme [1]. Here, radiation re-injected to the laser cavity interferes (‘mixes’) with the intra-cavity electric field, causing small variations in the fundamental laser parameters [2]. Of particular importance is the voltage perturbation induced by optical feedback. This can be used as a method of measuring the self-mixing effect through monitoring the terminal voltage of the device, and is dependent on the external cavity length and lasing frequency. As such, interferometric fringes can be acquired in a SM system by simply changing the external cavity length. In this work we demonstrate the use of SM interferometry for performing spectral characterisation of a multi-mode THz QCL in a scheme that offers much reduced experimental complexity, compared with typical Fourier Transform infrared spectroscopy (FTIR) systems.

Published
2016

31. Effect of a current blocking barrier on a 2–6 μm p-GaAs/AlGaAs heterojunction infrared detector

Author

Chauhan, D, Perera, AGU, Li, LH, Chen, L, and Linfield, EH

Abstract

We report the performance of a 30 period p-GaAs/AlxGa1 − xAs heterojunction photovoltaic infrared detector, with graded barriers, operating in the 2–6 μm wavelength range. Implementation of a current blocking barrier increases the specific detectivity (D*) under dark conditions by two orders of magnitude to ∼1.9 × 1011 Jones at 2.7 μm, at 77 K. Furthermore, at zero bias, the resistance-area product (R 0 A) attains a value of ∼7.2 × 108 Ω cm2, a five orders enhancement due to the current blocking barrier, with the responsivity reduced by only a factor of ∼1.5.

Published
2016

32. DOT associated with reduced all-cause mortality among tuberculosis patients in Taipei, Taiwan, 2006–2008

Author

Timothy C. Rodwell, Shih Hc, Chuang P, Yen My, Yung-Feng Yen, Li Lh, Shie Yh, Richard S. Garfein, and Hu Bs

Subjects
Male, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Tuberculosis, Population, Antitubercular Agents, Taiwan, Article, Risk Factors, Cause of Death, Humans, Medicine, education, Directly Observed Therapy, Aged, Retrospective Studies, Cause of death, education.field_of_study, business.industry, Transmission (medicine), Incidence (epidemiology), Mortality rate, Retrospective cohort study, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, Infectious Diseases, Female, business, Follow-Up Studies
Abstract

Tuberculosis (TB) remains a common and deadly disease globally. Approximately two billion people are latently infected with TB, and there are almost two million deaths annually due to active disease. In 2009, there were 9.4 million new TB cases, of which 3.3 million (35%) occurred in the South-East Asia region.1 Of all reportable infectious diseases in Taiwan, TB has for decades been the most prevalent and significant.2 From 1990 to 2005, TB incidence in Taiwan almost doubled, from 40 cases per 100 000 population to 72/100 000,2 and over 60% of TB treatment ‘failures’ were shown to be caused by death during treatment rather than defaulting on treatment.2 After the World Health Organization (WHO) introduced the ‘Plan to Stop TB’ in 2006,3 with proposals to halve TB incidence by 2015, the Taiwan Centers for Disease Control (CDC) adopted an aggressive strategy for TB control centred firmly on the implementation of directly observed treatment short course (DOTS) in the hope that increased monitoring would reduce both transmission of new cases and TB mortality.2 Directly observed treatment (DOT) was not previously a component of TB control policy in Taiwan, and when the DOTS strategy was implemented by the Taiwan CDC, TB patients at greatest risk for transmitting TB and with the most severe disease (e.g., those with positive acid-fast bacilli [AFB] smear or TB culture) were initially preferentially assigned to DOT.2 While the WHO endorses DOT, which stipulates that every dose of TB medication be observed by a health professional or designee to increase adherence, it has had variable effectiveness on TB treatment outcomes when put into practice.4–12 A Cochrane review of DOT in 2009 concluded that there were no statistically significant differences in treatment outcomes between TB patients on DOT and those using self-administered therapy (SAT).13 While the studies reviewed controlled for potential confounders, some null findings could have resulted from selection bias and residual confounding. To determine whether patients receiving DOT had lower all-cause mortality than those treated with SAT, we compared all-cause mortality rates among TB patients receiving TB treatment via DOT vs. SAT between 2006 and 2008 in Taipei City, the second largest city in Taiwan. We hypothesised that after accounting for confounding variables, patients on DOT would have lower all-cause mortality than those on SAT.

Published
2012

33. The MBE growth and optimization of high performance terahertz frequency quantum cascade lasers

Author

Li, LH, Zhu, JX, Chen, L, Davies, AG, and Linfield, EH

Abstract

The technique of molecular beam epitaxy has recently been used to demonstrate the growth of terahertz frequency GaAs/AlGaAs quantum cascade lasers (QCL) with Watt-level optical output powers. In this paper, we discuss the critical importance of achieving accurate layer thicknesses and alloy compositions during growth, and demonstrate that precise growth control as well as run-to-run growth reproducibility is possible. We also discuss the importance of minimizing background doping level in maximizing QCL performance. By selecting high-performance active region designs, and optimizing the injection doping level and device fabrication, we demonstrate total optical (two-facet) output powers as high as 1.56 W.

Published
2015

34. Expression of dopamine transporter in the different cerebral regions of methamphetamine-dependent rats

Author

Feng Zt, Zhang D, David T. Yew, Wan J, Yang P, Yu Y, Wang Th, Hong Sj, Zhang Lh, and Li Lh

Subjects
Male, medicine.medical_specialty, Substance-Related Disorders, Health, Toxicology and Mutagenesis, Dopamine Agents, Hippocampus, Substantia nigra, Striatum, Nucleus accumbens, Toxicology, Methamphetamine, Rats, Sprague-Dawley, Internal medicine, medicine, Animals, Dopamine transporter, Messenger RNA, Dopamine Plasma Membrane Transport Proteins, biology, Behavior, Animal, Brain, General Medicine, Conditioned place preference, Endocrinology, nervous system, Anesthesia, biology.protein, Female, medicine.drug
Abstract

Objectives: To observe the expression of the dopamine transporter (DAT) in six cerebral regions of a methamphetamine (MA)-dependent rat, which were frontal cortex, nucleus accumbens septi, striatum, hippocampus, substantia nigra and ventral tegmental area. Methods: The rats were administrated intraperitoneally with 10 mg/kg/day of MA for 10 days consecutively; the behaviour changes were measured via the conditioned place preference (CPP), and the scores of stereotyped behaviour (SB) were used to confirm animal addiction. Then, the animals were further injected with MA respectively for 1, 2, 4 and 8 weeks to establish different periods of MA-dependent models. The expressions of DAT and DAT messenger RNA in six cerebral regions were detected. Results: The results of CPP and SB scores were significant different when comparing all four experimental groups with the control group ( p < 0.05). Comparing between different experimental groups, the expression of DAT mainly decreased and had dynamic changes in the same regions ( p < 0.05). Comparing the different regions with each other in the same experimental group, the expression of DAT also had significant difference in several regions p < 0.05). Conclusions: The expression of DAT mainly decreased and had different in the six cerebral regions at the same MA-dependent time period as well as at different time periods in the same cerebral region. It was speculated that DAT might play a crucial role in the mechanism of MA dependence.

Published
2014

35. Quantum Emission from Defects in Single-Crystalline Hexagonal Boron Nitride

Author

Tran, TT, Zachreson, C, Berhane, AM, Bray, K, Sandstrom, RG, Li, LH, Taniguchi, T, Watanabe, K, Aharonovich, I, Toth, M, Tran, TT, Zachreson, C, Berhane, AM, Bray, K, Sandstrom, RG, Li, LH, Taniguchi, T, Watanabe, K, Aharonovich, I, and Toth, M

Abstract

© 2016 American Physical Society. Bulk hexagonal boron nitride (hBN) is a highly nonlinear natural hyperbolic material that attracts major attention in modern nanophotonics applications. However, studies of its optical properties in the visible part of the spectrum and quantum emitters hosted by bulk hBN have not been reported to date. In this work, we study the emission properties of hBN crystals in the red spectral range using sub-band-gap optical excitation. Quantum emission from defects is observed at room temperature and characterized in detail. Our results advance the use of hBN in quantum nanophotonics technologies and enhance our fundamental understanding of its optical properties.

Published
2016

36. Electron beam directed etching of hexagonal boron nitride

Author

Elbadawi, C, Tran, TT, Kolíbal, M, Šikola, T, Scott, J, Cai, Q, Li, LH, Taniguchi, T, Watanabe, K, Toth, M, Aharonovich, I, Lobo, C, Elbadawi, C, Tran, TT, Kolíbal, M, Šikola, T, Scott, J, Cai, Q, Li, LH, Taniguchi, T, Watanabe, K, Toth, M, Aharonovich, I, and Lobo, C

Abstract

© 2016 The Royal Society of Chemistry. Hexagonal boron nitride (hBN) is a wide bandgap van der Waals material with unique optical properties that make it attractive for two dimensional (2D) photonic and optoelectronic devices. However, broad deployment and exploitation of hBN is limited by alack of suitable material and device processing and nano prototyping techniques. Here we present a high resolution, single step electron beam technique for chemical dry etching of hBN. Etching is achieved using H2O as a precursor gas, at both room temperature and elevated hBN temperatures. The technique enables damage-free, nano scale, iterative patterning of supported and suspended 2D hBN, thus opening the door to facile fabrication of hBN-based 2D heterostructures and devices.

Published
2016

37. Study on extraction process of active ingredients from Akebia stem and analysis of their anti-gastric cancer activity

Author

Lu, YZ, Ye, HM, Zeng, HZ, Li, LH, Wu, GY, and Liu, GY

Subjects
SGC-7901 cell, Akebia trifoliata (Thunb.), extraction process
Abstract

The study investigated the extraction process of active ingredients from akebia stem and an analysis of their anti-gastric cancer activity. Three different extraction methods were used to obtain extracts, namely the decoction method (group A), reflux extraction method (group B), and maceration method (group C), of which reflux extraction method and maceration method used ethanol as the extraction solvent, while decoction method used distilled water for extraction. The differences in anti-gastric cancer activity of the three extracts were compared. MTT assay was used to test and compare the inhibitory effects of extracts obtained in A, B, and C groups on gastric cancer cells. The results showed that the dry extract obtained by heat reflux extraction with “water-ethanol” ratio of 1:2, extractant volume of 70 ml, with ethanol as extraction solvent presented the best inhibitory activity on gastric cancer SGC-7901 cells in this study. Its inhibitory effect did not change over time, and was directly proportional to the concentration.Keywords: SGC-7901 cell, Akebia trifoliata (Thunb.), extraction process

Published
2013

38. Three-section terahertz quantum cascade lasers with externally biased photonic lattices

Author

Kundu, I, Dean, P, Li, LH, Valavanis, A, Khanna, SP, Evans, CA, Cunningham, JE, Linfield, EH, and Davies, AG

Subjects
Physics::Optics
Abstract

Single-mode (SM) operation of terahertz (THz)-frequency quantum cascade lasers (QCLs) is essential for gas sensing and for their use as local oscillators. Whilst such SM operation has been demonstrated previously using distributed feedback gratings and photonic lattices (PLs), an ability to tune SM THz QCLs electronically would be highly desirable for many applications. This work investigates the electronic properties of multiple segment QCLs, and explores possible electronic tuning mechanisms. We have fabricated THz QCLs with PL gratings. Our THz QCLs, based on a bound-to-continuum active region design, were processed into 150-μm-wide surface-plasmon ridge waveguides with lengths 2.5–4.5 mm. The upper waveguide was then patterned into three sections. The outer sections were fully metallised with gold. In the central 530-μm-long section, however, the top n-doped layer was etched away and metallic PLs fabricated using electron-beam lithography, with grating pitch between 14.60 and 15.65 μm. In each device, both the PL and the outer sections were bonded separately to allow independent biasing. Devices were cooled in a continuous-flow helium cryostat and emission spectra measured using a Fourier-transform infrared spectrometer. Standard (unpatterned) devices lased with multiple Fabry–Pérot modes in the range 2.70–2.83 THz, whilst single mode emission was observed for devices patterned with a PL (Fig. 2). The emission spectra recorded from devices with PLs of different grating pitch showed stop-band behaviour, with the experimentally-determined stop-band bandwidth of around 25 GHz agreeing with the value of 23 GHz calculated using finite-element modelling. Light-output–current–voltage (LIV) characteristics were acquired under different configurations, including the central PL sections both biased and unbiased. An equivalent circuit model describing the electronic properties of the three-section devices was developed, and was found to reproduce the experimental observations well.

Published
2013

39. Estimating zero-plane displacement height and aerodynamic roughness length using synthesis of LiDAR and SPOT-5 data

Author

Tian, X, Li, ZY, van der Tol, C, Su, Z, Li, X, He, QS, Bao, YF, Chen, EX, and Li, LH

Subjects
Geological & Geomatics Engineering
Abstract

In this study, a combination of low and high density airborne LiDAR and satellite SPOT-5 HRG data were used in conjunction with ground measurements of forest structure to parameterize four models for zero-plane displacement height d(m) and aerodynamic roughness length z0m(m), over cool-temperate forests in Heihe River basin, an arid region of Northwest China. For the whole study area, forest structural parameters including tree height (Ht) (m), first branch height (FBH) (m), crown width (CW) (m) and stand density (SD)(treesha-1) were derived by stepwise multiple linear regressions of ground-based forest measurements and height quantiles and fractional canopy cover (fc) derived from the low density LiDAR data. The high density LiDAR data, which covered a much smaller area than the low density LiDAR data, were used to relate SPOT-5's reflectance to the effective plant area index (PAIe) of the forest. This was done by linear spectrum decomposition and Li-Strahler geometric-optical models. The result of the SPOT-5 spectrum decomposition was applied to the whole area to calculate PAIe (and leaf area index LAI). Then, four roughness models were applied to the study area with these vegetation data derived from the LiDAR and SPOT-5 as input. For validation, measurements at an eddy covariance site in the study area were used. Finally, the four models were compared by plotting histograms of the accumulative distribution of modeled d and z0m in the study area. The results showed that the model using by frontal area index (FAI) produced best d estimate, and the model using both LAI and FAI generated the best z0m. Furthermore, all models performed much better when the representative tree height was Lorey's mean height instead of using an arithmetic mean. © 2011 Elsevier Inc.

Published
2011

41. Mode hybridization in photonic crystal molecules

Author

Vignolini S., Riboli F., Intonti F., Wiersma D., Balet L., Li LH., Francardi M., Gerardino A., Fiore A., and Giurioli M.

Subjects
photonic crystals, Physics::Optics, polarisation
Abstract

A complete control of the coupling between the modes of two photonic crystal microcavities is obtained by using a combination of several local tuning techniques. By a local and controlled modification of one cavity we are able to bring into resonance modes with a different polarization and spatial distribution, producing heteroatomic photonic molecules. Clear anticrossing is observed, denoting the mode hybridization which is in a very good agreement with finite difference time domain calculations.

Published
2010

42. High-efficient production of boron nitride nanosheets via an optimized ball milling process for lubrication in oil

Author

Deepika, Li,LH, Glushenkov,AM, Hait,SK, Hodgson,P, Chen,Y, Deepika, Li,LH, Glushenkov,AM, Hait,SK, Hodgson,P, and Chen,Y

Abstract

Although tailored wet ball milling can be an efficient method to produce a large quantity of two-dimensional nanomaterials, such as boron nitride (BN) nanosheets, milling parameters including milling speed, ball-to-powder ratio, milling ball size and milling agent, are important for optimization of exfoliation efficiency and production yield. In this report, we systematically investigate the effects of different milling parameters on the production of BN nanosheets with benzyl benzoate being used as the milling agent. It is found that small balls of 0.1-0.2 mm in diameter are much more effective in exfoliating BN particles to BN nanosheets. Under the optimum condition, the production yield can be as high as 13.8% and the BN nanosheets are 0.5-1.5 μm in diameter and a few nanometers thick and of relative high crystallinity and chemical purity. The lubrication properties of the BN nanosheets in base oil have also been studied. The tribological tests show that the BN nanosheets can greatly reduce the friction coefficient and wear scar diameter of the base oil.

Published
2014

43. Hydrogen evolution by a metal-free electrocatalyst

Author

Zheng,Y, Jiao,Y, Zhu,Y, Li,LH, Han,Y, Chen,Y, Du,A, Jaroniec,M, Qiao,SZ, Zheng,Y, Jiao,Y, Zhu,Y, Li,LH, Han,Y, Chen,Y, Du,A, Jaroniec,M, and Qiao,SZ

Abstract

Electrocatalytic reduction of water to molecular hydrogen via the hydrogen evolution reaction may provide a sustainable energy supply for the future, but its commercial application is hampered by the use of precious platinum catalysts. All alternatives to platinum thus far are based on nonprecious metals, and, to our knowledge, there is no report about a catalyst for electrocatalytic hydrogen evolution beyond metals. Here we couple graphitic-carbon nitride with nitrogen-doped graphene to produce a metal-free hybrid catalyst, which shows an unexpected hydrogen evolution reaction activity with comparable overpotential and Tafel slope to some of well-developed metallic catalysts. Experimental observations in combination with density functional theory calculations reveal that its unusual electrocatalytic properties originate from an intrinsic chemical and electronic coupling that synergistically promotes the proton adsorption and reduction kinetics.

Published
2014

44. Observation of active sites for oxygen reduction reaction on nitrogen-doped multilayer graphene

Author

Xing,T, Zheng,Y, Li,LH, Cowie,BC, Gunzelmann,D, Qiao,SZ, Huang,S, Chen,Y, Xing,T, Zheng,Y, Li,LH, Cowie,BC, Gunzelmann,D, Qiao,SZ, Huang,S, and Chen,Y

Abstract

Active sites and the catalytic mechanism of nitrogen-doped graphene in an oxygen reduction reaction (ORR) have been extensively studied but are still inconclusive, partly due to the lack of an experimental method that can detect the active sites. It is proposed in this report that the active sites on nitrogen-doped graphene can be determined via the examination of its chemical composition change before and after ORR. Synchrotron-based X-ray photoelectron spectroscopy analyses of three nitrogen-doped multilayer graphene samples reveal that oxygen reduction intermediate OH(ads), which should chemically attach to the active sites, remains on the carbon atoms neighboring pyridinic nitrogen after ORR. In addition, a high amount of the OH(ads) attachment after ORR corresponds to a high catalytic efficiency and vice versa. These pinpoint that the carbon atoms close to pyridinic nitrogen are the main active sites among the different nitrogen doping configurations.

Published
2014

45. Simulation of diurnal variations of CO2, water and heat fluxes over winter wheat with a model coupled photosynthesis and transpiration

Author

Wang, J, Yu, Q, Li, J, Li, LH, Li, XG, Yu, GR, and Sun, XM

Subjects
Meteorology & Atmospheric Sciences
Abstract

A model was developed that couples canopy photosynthesis and transpiration of winter wheat. The model combined a two-layer evapotranspiration model with a coupled photosynthesis-stomatal conductance model to study the diurnal variations of CO2, water and heat fluxes of winter wheat. Field experiments were conducted in Yucheng Comprehensive Experimental Station in the North China Plain to evaluate the model. Half-hourly data of weather variables and CO2, water and heat fluxes were measured by the eddy covariance method in 2002-2003. An analysis of measured flux data showed that there was an evident midday depression of photosynthesis, caused by stomatal closure due to high vapor water deficit and canopy temperature though the soil was well irrigated. There was a close agreement between simulated and measured net radiation, CO2 flux, sensible and latent heat fluxes, which proved the predictive power of the coupled photosynthesis and transpiration model. The response of CO2 flux, canopy conductance and latent heat flux to changes in climatic factors was discussed, which indicated the model could be used to predict CO2, water and heat fluxes of wheat not only in the North China Plain, but also in other climatic regions in China. © 2006 Elsevier B.V. All rights reserved.

Published
2006

48. Three-dimensional simulations of the upper radiation-convection transition layer in subgiant stars

Author

Robinson, FJ, Demarque, P., Li, LH, Sofia, S., Kim, YC, Chan, KL, Guenther, DB, Robinson, FJ, Demarque, P., Li, LH, Sofia, S., Kim, YC, Chan, KL, and Guenther, DB

Abstract

This paper describes three-dimensional (3D) large eddy simulations of stellar surface convection using realistic model physics. The simulations include the present Sun, a subgiant of one solar mass and a lower-gravity subgiant, also of one solar mass. We examine the thermal structure (superadiabaticity) after modification by 3D turbulence, the overshoot of convective motions into the radiative atmosphere and the range of convection cell sizes. Differences between models based on the mixing length theory (MLT) and the simulations are found to increase significantly in the more evolved stages as the surface gravity decreases. We find that the full width at half maximum (FWHM) of the turbulent vertical velocity correlation provides a good objective measure of the vertical size of the convective cells. Just below the convection surface, the FWHM is close to the mean vertical size of the granules and 2 x FWHM is close to the mean horizontal diameter of the granules. For the Sun, 2 x FWHM = 1200 km, a value close to the observed mean granule size. For all the simulations, the mean horizontal diameter is close to 10 times the pressure scaleheight at the photospheric surface, in agreement with previous work.

Published
2004

49. Three-dimensional convection simulations of the outer layers of the Sun using realistic physics

Author

Robinson, FJ, Demarque, P., Li, LH, Sofia, S., Kim, YC, Chan, KL, Guenther, DB, Robinson, FJ, Demarque, P., Li, LH, Sofia, S., Kim, YC, Chan, KL, and Guenther, DB

Abstract

This paper describes a series of three-dimensional simulations of shallow inefficient convection in the outer layers of the Sun. The computational domain is a closed box containing the convection-radiation transition layer, located at the top of the solar convection zone. The most salient features of the simulations are that: (i) the position of the lower boundary can have a major effect on the characteristics of solar surface convection (thermal structure, kinetic energy and turbulent pressure); (ii) the width of the box has only a minor effect on the thermal structure, but a more significant effect on the dynamics (rms velocities); (iii) between the surface and a depth of 1 Mm, even though the density and pressure increase by an order of magnitude, the vertical correlation length of vertical velocity is always close to 600 km; (iv) in this region the vertical velocity cannot be scaled by the pressure or the density scaleheight; this casts doubt on the applicability of the mixing length theory, not only in the superadiabatic layer, but also in the adjacent underlying layers; (v) the final statistically steady state is not strictly dependent on the initial atmospheric stratification.

Published
2003

50. Effect of ion-induced damage on GaNAs/GaAs quantum wells grown by plasma-assisted molecular beam epitaxy

Author

Li, LH, Pan, Z., Zhang, W., Lin, YW, Wang, XY, Wu, RH, Ge, WK, Li, LH, Pan, Z., Zhang, W., Lin, YW, Wang, XY, Wu, RH, and Ge, WK

Abstract

The effect of ion-induced damage on GaNAs/GaAs quantum wells (QWs) grown by molecular beam epitaxy employing a DC plasma as the N source was investigated. Ion-induced damage results in: (i) an observed disappearance of pendellosung fringes in the X-ray diffraction pattern of the sample; (ii) a drastic decrease in intensity and a broadening in the full-width at half-maximum of photoluminescence spectra. It was shown that ion-induced damage strongly affected the bandedge potential fluctuations of the QWs. The bandedge potential fluctuations for the samples grown with and without ion removal magnets (IRMs) are 44 and 63 meV, respectively. It was found that the N-As atomic interdiffusion at the interfaces of the QWs was enhanced by the ion damage-induced defects. The estimated activation energies of the N-As atomic interdiffusion for the samples grown with and without IRMs are 3.34 and 1.78 eV, respectively. (C) 2001 Elsevier Science B.V. All rights reserved.

Published
2001

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