Identification of Halohydrin Dehalogenase Mutants that Resist COBE Inhibition

Shao-Yun Chen,Xiu-Juan He,Jian-ping Wu,Gang Xu,Li-Rong Yang 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.1

The biocatalytic cascade conversion of ethyl4-chloroacetoacetate (COBE) to ethyl (R)-4-cyano-3-hydroxybutyrate ((R)-HN) for the preparation of atorvastatinrepresents significant economic and environmental benefits,and is catalyzed by alcohol dehydrogenase and halohydrindehalogenase (HHDH). However, as the activity of HHDHis inhibited by COBE, the cascade reaction is an inefficientone-pot reaction. In this study, substrate inhibition kineticsanalysis was performed and the inhibition by COBE wasfound to be competitive reversible inhibition. Molecularsimulation analysis was used to determine the inhibitionmechanism by COBE. The results showed that COBEbound to the active center of HHDH via the formation ofhydrogen bonds with the OH groups of S132 and Y145. Site saturation mutagenesis of residues around the activesite and at the entrance of the access tunnel was performed,and two target mutant residues were identified, F136 andW249. Small focused mutagenesis on these two residueswas performed and the F136V/W249F mutant wassuccessfully found to relieve the activity inhibition ofHHDH by COBE. The half inhibiting concentration ofmutant F136V/W249F was found to be 20-fold higher thanwild-type HHDH. The efficiency of the multi-enzymaticone-pot system for the synthesis of (R)-HN from COBEusing mutant F136V/W249F was improved significantly.

Recent progresses in marine microbial-derived antiviral natural products

Yun‑Fei Teng,Li Xu,Mei‑Yan Wei,Chang‑Yun Wang,Yu‑Cheng Gu,Chang‑Lun Shao 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.12

Viruses have always been a class of pathogenicmicroorganisms that threaten the health and safety of humanlife worldwide. However, for a long time, the treatment ofviral infections has been slow to develop, and only a fewantiviral drugs have been using clinically. Compared withthese from terrestrial environments, marine-derived microorganismscan produce active substances with more novelstructures and unique functions. From 2015 to 2019, 89antiviral compounds of 8 structural classes have been isolatedfrom marine microorganisms, of which 35 exhibit anti-H1N1 activity. This review surveys systematically marinemicrobial-derived natural products with antiviral activityand illustrates the impact of these compounds on antiviraldrug discovery research.

Evidence Based Analysis of Cisplatin for Treating Patients with Cutaneous Squamous Cell Carcinoma

Shao, Xiao-Hong,Xu, Yun-Sheng,Zhang, Xue-Qi,Li, Wen-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: This analysis was conducted to evaluate the efficacy and safety of cisplatin based chemotherapy for treating patients with cutaneous squamous cell carcinoma. Methods: Clinical studies evaluating the efficacy and safety of cisplatin based regimens on response and safety for patients with cutaneous squamous cell carcinoma were identified using a predefined search strategy. Pooled response rates (RR) of treatment were calculated. Results: In cisplatin based regimens, 4 clinical studies which including 50 patients with advanced cutaneous squamous cell carcinoma were considered eligible for inclusion. Regimens included cisplatin, doxorubicin, or vindesine. Pooled analysis suggested that, in all patients, the pooled RR was 60% (30/50) in cisplatin based regimens. Nausea and vomiting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred with the cisplatin based treatments. Conclusion: Evidence based analysis suggests that cisplatin based regimens are associated with a good response rate and acceptable toxicity for treating patients with cutaneous squamous cell carcinoma.

Transformerless Three-Level DC-DC Buck Converter with a High Step-Down Conversion Ratio

Yun Zhang,Xing-tao Sun,Yi-feng Wang,Hong-jun Shao 전력전자학회 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.1

For high power high step-down dc-dc conversion applications, conventional three-level dc-dc converters are subject to extreme duty cycles or increased volume and cost due to the use of transformers. In this paper, a transformerless three-level dc-dc buck converter with a high step-down conversion ratio is proposed. The converter comprises two asymmetrical half bridges, which are of the neutral point clamped structures. Therefore, the output pulse voltage of the converter can be obtained in terms of the voltage difference between the two half bridges. In order to realize harmonious switching of the converter, a modulation strategy with capacitor voltages self balance is presented. According to the deduced output dc voltage function, transformerless operation without extreme duty cycles can be implemented. Experimental results from a 1kW prototype verify the validity of the proposed converter. It is suitable for ship electric power distribution systems.

Anomalous Propagation Characteristics of an Airy Beam in Nonlocal Nonlinear Medium

Yun-Long Wu,Qin Ye,Li Shao 한국광학회 2021 Current Optics and Photonics Vol.5 No.2

The anomalous propagation characteristics of a single Airy beam in nonlocal nonlinear medium are investigated by utilizing the split-step Fourier-transform method. We show that besides the normal straight propagation trajectory, the breathing solitons formed by the interaction between Airy beam and nonlocal nonlinear medium can propagate along the sinusoidal trajectory, and the anomalous trajectory can be modulated arbitrarily by altering the initial amplitude and the nonlocal nonlinear coefficient. In addition, the initial amplitude and the nonlocal nonlinear coefficient can have inverse impacts on the formation and transformation of the equilibrium state of spatial solitons, when the two parameters are larger than certain values. Therefore, the reversible transformation of the evolution dynamics of two soliton states can be realized by adjusting those two parameters properly. Finally, it is shown that the propagation properties of the solitons formed by the interaction between Airy beam and nonlocal nonlinear medium can be controlled arbitrarily, by adjusting the distribution factor and nonlocal coefficient.

The Prognostic Value of 18F-Fluorodeoxyglucose PET/CT in the Initial Assessment of Primary Tracheal Malignant Tumor: A Retrospective Study

Shao Dan,Gao Qiang,Cheng You,Du Dong-Yang,Wang Si-Yun,Wang Shu-Xia 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.3

Objective: To investigate the potential value of 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the survival of patients with primary tracheal malignant tumors. Materials and Methods: An analysis of FDG PET/CT findings in 37 primary tracheal malignant tumor patients with a median follow-up period of 43.2 months (range, 10.8–143.2 months) was performed. Cox proportional hazards regression analyses were used to assess the associations between quantitative 18F-FDG PET/CT parameters, other clinic-pathological factors, and overall survival (OS). A risk prognosis model was established according to the independent prognostic factors identified on multivariate analysis. A survival curve determined by the Kaplan-Meier method was used to assess whether the prognosis prediction model could effectively stratify patients with different risks factors. Results: The median survival time of the 37 patients with tracheal tumors was 38.0 months, with a 95% confidence interval of 10.8 to 65.2 months. The 3-year, 5-year and 10-year survival rate were 54.1%, 43.2%, and 16.2%, respectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value, age, pathological type, extension categories, and lymph node stage were included in multivariate analyses. Multivariate analysis showed MTV (p = 0.011), TLG (p = 0.020), pathological type (p = 0.037), and extension categories (p = 0.038) were independent prognostic factors for OS. Additionally, assessment of the survival curve using the Kaplan-Meier method showed that our prognosis prediction model can effectively stratify patients with different risks factors (p < 0.001). Conclusion: This study shows that 18F-FDG PET/CT can predict the survival of patients with primary tracheal malignant tumors. Patients with an MTV > 5.19, a TLG > 16.94 on PET/CT scans, squamous cell carcinoma, and non-E1 were more likely to have a reduced OS.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis

Yun-Ru Chen,Ruo-Tong Zhao,Yi-Fang Xu,Yin-Jie Ma,Shao-Bo Hu,Xue-Hui Wang,Bing-Bing Fan,Yan-Ji Zhou,Yu-Bei Huang,Nicola Robinson,Jian-ping Liu,Zhao-Lan Liu 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.4

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21–1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20–2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16–1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo

Ge, Yun-Fei,Sun, Jun,Jin, Chun-Jie,Cao, Bo-Qiang,Jiang, Zhi-Feng,Shao, Jun-Fei Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.

Transformerless Three-Level DC-DC Buck Converter with a High Step-Down Conversion Ratio

Zhang, Yun,Sun, Xing-Tao,Wang, Yi-Feng,Shao, Hong-Jun The Korean Institute of Power Electronics 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.1

For high power high step-down dc-dc conversion applications, conventional three-level dc-dc converters are subject to extreme duty cycles or increased volume and cost due to the use of transformers. In this paper, a transformerless three-level dc-dc buck converter with a high step-down conversion ratio is proposed. The converter comprises two asymmetrical half bridges, which are of the neutral point clamped structures. Therefore, the output pulse voltage of the converter can be obtained in terms of the voltage difference between the two half bridges. In order to realize harmonious switching of the converter, a modulation strategy with capacitor voltages self balance is presented. According to the deduced output dc voltage function, transformerless operation without extreme duty cycles can be implemented. Experimental results from a 1kW prototype verify the validity of the proposed converter. It is suitable for ship electric power distribution systems.

Fast Motion Estimation Based on Motion Speed and Multiple Initial Center Point Prediction

팽소호(Shao-Hu Peng),뮤잠멜(Khairul Muzzammil Saipullah),윤병춘(Byung-Choon Yun),김덕환(Deok-Hwan Kim) 한국정보과학회 2010 한국정보과학회 학술발표논문집 Vol.37 No.1A

This paper proposes a fast motion estimation algorithm based on motion speed and multiple initial center points. The proposed method predicts initial search points by means of the spatio-temporal neighboring motion vectors. A dynamic search pattern based on motion speed and the predicted initial center points is proposed to quickly obtain the motion vector. Due to the usage of the spatio-temporal information and the dynamic search pattern, the proposed method greatly accelerates the search speed while maintaining a good predicted image quality. Experimental results show that the proposed method has a good predicted image quality in terms of PSNR with less search time as compared to the Full Search, New Three-Step Search, and Four-Step Search.