Improvement of FK506 Production by Selection of 4-Aminobutyric Acid-tolerant Mutant and Optimization of its Fermentation Using Response Surface Methodology

Yang, Tianyi,Li, Jiaojiao,Li, Liangzhi,Zhang, Haiyang,Ma, Jing,Chen, Zhi,Hu, Cuiying,Ju, Xin,Fu, Jiaolong 한국응용생명화학회 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.6

Tacrolimus (FK506), a 23-membered polyketide macrolide with immunosuppressant activity, can be produced by Streptomyces tsukubaensis. We studied a variety of mutant strains of S. tsukubaensis for the microbial production of FK506. The best strain (CZ-19) was obtained from the parent strain LLZ-1 by nitrosoguanidine mutation and 4-Aminobutyric acid (FK506 precursor structure analogs) adaption. In the shake-flask experiments, titer of FK506 by CZ-19 was 532.44 mg/L, increased by 65.13% compared to that of the parent strain. Through single factor experiments and response surface methodology, we further optimized the medium for improved FK506 production by CZ-19 in shake flask culture. The optimal medium for enhanced FK506 production was as follows: 17.19 g/L corn starch, 21.78 g/L glucose, 8.06 g/L peptone, and 18.98 mg/L 4-aminobutyric acid. The predicted FK506 titer was 906.49 mg/L, and the experimental data confirmed the validity of the model. The present study demonstrates that S. tsukubaensis CZ-19 is a promising strain for industrial production of FK506.

Influence of oxygen equivalent on molten salt oxidation efficiency of mixed resin in Li2CO3-Na2CO3-K2CO3 melt

Xin Liu,Zi-Yu Liu,Yang-Hai Zheng,Yong-De Yan,Wen-Da Xu,Yun Xue,Yue-Lin Wang,Fu-Qiu Ma,Kai Zhu,Yu-Sheng Yang 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.120 No.-

The disposal of spent radioactive ion exchange resin generated during the operation of nuclear facilitieshas always been a conundrum. The molten salt oxidation (MSO) for the treatment of mixed resin (MR)shows obvious superiority. In this work, ternary carbonate (Li2CO3-Na2CO3-K2CO3) and MR was usedas the molten salt system and the oxidation target, respectively. The oxidation behavior of MR was analyzedby varying the temperature and oxygen equivalent during the MSO process. By studying the effectof different oxygen equivalents on the oxidation efficiency, the oxygen equivalent of 125% could make theoxidation efficiency of MR reach 99.99% at 800 C. The composition of C, N and S containing exhaust gasproduced through MSO process of MR with temperature were almost consistent with the simulationresults. The exhaust gas was successfully adsorbed by molten carbonate to produce nitrate and sulfurcompounds. The carbonate has good absorption to harmful gases such as SO2, CO, NO, etc. The contentof SO2 from the highest 0.32% to 0, and 71.23% of sulfur in MR was trapped by molten carbonate asthe form of sulfate. This work has important implications for reducing the potential harm of radioactivewaste resin to the environment.

ELECTRIC-HYDRAULIC COMPOUND CONTROL ANTI-LOCK BRAKING SYSTEM

Feng Yang,Xin Chen,Dong Guo,Mingmao Hu,Ziwen Liao,Zhongcheng Fu,Qingshan Gong 한국자동차공학회 2022 International journal of automotive technology Vol.23 No.6

An anti-lock control strategy for electric-hydraulic compound braking is proposed to improve the emergency braking safety of a hub motor electric vehicle. Based on the half-vehicle braking longitudinal dynamics model, the optimal control is solved to obtain the total braking torque corresponding to each wheel. A fuzzy algorithm is used to determine the proportion coefficient of the motor based on the battery state of charge coefficient (SOC) and the motor speed constraints on the motor braking, and the total braking torque is distributed. The hydraulic and motor braking torques obtained from the allocation are input as reference values to the electric-hydraulic compound braking system, and the output braking torque is fed back into the CarSim vehicle model. The proposed electric-hydraulic compound ABS control strategy is also validated in the co-simulation of CarSim and MATLAB/Simulink on high, medium and low adhesion road surfaces.

A Fast Rough Mode Decision Algorithm for HEVC

Wei-Xin Yao,Dan Yang,Gui-Fu Lu,Jun Wang 한국정보처리학회 2019 Journal of information processing systems Vol.15 No.3

HEVC is the high efficiency video coding standard, which provides better coding efficiency contrasted with theother video coding standard. But at the same time the computational complexity increases drastically. Thirtyfivekinds of intra-prediction modes are defined in HEVC, while 9 kinds of intra prediction modes are definedin H.264/AVC. This paper proposes a fast rough mode decision (RMD) algorithm which adopts the smoothnessof the up-reference pixels and the left-reference pixels to decrease the computational complexity. The three stepsearch method is implemented in RMD process. The experimental results compared with HM13.0 indicate thatthe proposed algorithm can save 39.7% of the encoding time, while Bjontegaard delta bitrate (BDBR) isincreased slightly by 1.35% and Bjontegaard delta peak signal-to-noise ratio (BDPSNR) loss is negligible.

A Clinical Study on Juheli (Recombinant Human Interleukin - 11) in the Second Prevention of Chemotherapy Induced Thrombocytopenia

Xiao, Yang,Liu, Jun,Huang, Xin-En,Guo, Jian-Xiong,Fu, Peng-Chao,Huang, Xiao-Hong,Zhou, Juan,Ye, Ai-Qin Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.2

Objective: to investigate the effect and side effects of recombinant human interleukin - 11 (rhIL - 11, in Chinese Juheli, produced by Qi Lu Biotechnology CO., LTD) in the second prevention of chemotherapy induced thrombocytopenia (CIT). Methods: Cancer patients with CIT were recruited and were treated with rhIL - 11 (treatment phase, TP), and in the following cycle, all these patients administered with rhIL - 11 24 hours immediately after chemotherapy (preventive treatment phase, PTP). Duration and severity of thrombocytopenia between two phases were compared. Results: for patients in TP or PTP, nadir values of platelet were ($29.28{\pm}20.08){\times}10^9/L$ and ($45.24{\pm}19.66){\times}10^9/L$, duration of thrombocytopenia in TP and PTP was ($11.52{\pm}4.33$) and ($8.20{\pm}+2.77$)days, recovery time was ($19.40{\pm}3.89$)and ($13.44{\pm}3.02$)days, duration of rhIL - 11 administration was ($10.68{\pm}2.46$)and ($6.28{\pm}1.77$)days, number of patients needing platelet infusion was 16and4 respectively, all differences were statistically significant (p value were 0.007, 0.002, 0.000, 0.000, 0.034 respectively). For TP and PTP, number of patients with hemorrhage was 8 and 4, duration of bleeding was ($5.00{\pm}0.82$) and ($4.50{\pm}0.71$) days respectively, with no statistically significant difference. Adverse reactions mainly included fever, edema, arrhythmia, joint pain, fatigue, skin rash, headache, dizziness, etc., all were not statistically significant between TP and PTP. Conclusion: rhIL - 11 could be well tolerated and is effective that could reduce the duration, severity of CIT, platelet transfusion, and incidence of bleeding, as well as shorten the recovery time, duration of rhIL - 11 administration. Thus, rhIL - 11 could be commended in the second prevention of CIT for patients with cancer.

Mechanical Resonance Suppression in Servo System Based on The Fractional Order Low-pass Filter

Ming Yang,Yongjian Fu,Xin Lv,Dianguo Xu 전력전자학회 2015 ICPE(ISPE)논문집 Vol.2015 No.6

The conventional filter method could effectively suppress resonance in servo system without backlash. But when the system contains backlash, the methods may fail. In this paper, a fractional order low-pass filter substitutes the integer order low-pass in a dual-inertia servo system with backlash to solve the problem. Fractional algorithm provides greater flexibility for robust control design, because it makes the order of the low-pass filter from integer domain to real-number domain. Fractional order low-pass filter can achieve a better tradeoff between robustness and resonance suppression by selecting the appropriate order. For implementation of the fractional order, Oustaloup recursive approximation method is introduced. Experimental results show that fractional-order low-pass filter can improve robustness while suppressing system resonance.

Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT

Shiyao Fu,Mingao Wang,Bin Li,Xu Li,Jianjun Cheng,Haitian Zhao,Hua Zhang,Aijun Dong,Weihong Lu,Xin Yang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. Methods A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV– Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. Results It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H2O overexpressed at the tumor site. Conclusions By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.

Improvement of FK506 Production by Selection of 4-Aminobutyric Acid-tolerant Mutant and Optimization of its Fermentation Using Response Surface Methodology

Tianyi Yang,Jiaojiao Li,Liangzhi Li,Haiyang Zhang,Jing Ma,Zhi Chen,Cuiying Hu,Xin Ju,Jiaolong Fu 한국응용생명화학회 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.6

Tacrolimus (FK506), a 23-membered polyketidemacrolide with immunosuppressant activity, can be produced byStreptomyces tsukubaensis. We studied a variety of mutant strainsof S. tsukubaensis for the microbial production of FK506. Thebest strain (CZ-19) was obtained from the parent strain LLZ-1 bynitrosoguanidine mutation and 4-Aminobutyric acid (FK506precursor structure analogs) adaption. In the shake-flask experiments,titer of FK506 by CZ-19 was 532.44 mg/L, increased by 65.13%compared to that of the parent strain. Through single factorexperiments and response surface methodology, we furtheroptimized the medium for improved FK506 production by CZ-19in shake flask culture. The optimal medium for enhanced FK506production was as follows: 17.19 g/L corn starch, 21.78 g/Lglucose, 8.06 g/L peptone, and 18.98 mg/L 4-aminobutyric acid. The predicted FK506 titer was 906.49 mg/L, and the experimentaldata confirmed the validity of the model. The present studydemonstrates that S. tsukubaensis CZ-19 is a promising strain forindustrial production of FK506.

Numerical Simulation and Experimental Study on Flow Forming of Laser Concave–Convex Microtexture of Cr12 Steel Surface

Xiping Yang,Yonghong Fu,Xin Kuang 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.10

In this paper, Cr12 steel was taken as the research object, and laser micro melting model was established in comsol softwarebased on physical equations such as laser heat source, convection heat transfer, evaporation mobility, recoil pressure,Marangoni effect. The forming mechanism and evolution law of concave–convex microtexture morphology were studiedby numerical simulation. The research reveals the changing process of the velocity of the flow field inside the material duringthe surface deformation. In addition, it can be found from the temperature field changes under different power that thehigher the power is, the faster the surface temperature of Cr12 material increases in the process of thermal deformation. Andthe hardness of the microtexture was greatly improved after the material experienced sudden heat and cold in a very shorttime. By comparing the numerical simulation results and the experimental results, it can be found that with the increase ofpower, the height, depth and diameter of the concave–convex microtexture morphology all show an increasing trend, andthe surface geometry obtained through numerical simulation matches well with the experimental results. It indicates thatthe numerical simulation has high feasibility and can effectively reflect the forming process and morphology of concaveconvexmicrotexture.

Association Between MDM2 SNP309 T>G and Risk of Gastric Cancer: A Meta-analysis

Tian, Xin,Tian, Ye,Ma, Ping,Sui, Cheng-Guang,Meng, Fan-Dong,Li, Yan,Fu, Li-Ye,Jiang, Tao,Wang, Yang,Ji, Fu-Jian,Fang, Xue-Dong,Jiang, You-Hong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: As a negative regulator of P53, MDM2 plays an important role in carcinogenesis; a polymorphism in its promoter region. SNP309 T>G, is known to increase the expression of MDM2, thus being considered related to higher susceptibility to neoplasia. However, no agreement has been achieved regarding its effects on gastric cancer. Methods: The present systematic meta-analysis was performed based on comprehensive literature search from Pubmed, Web of science and CBM databases. Results: It was suggested from 6 independent studies that the GG genotype is associated with a significantly increased risk of gastric cancer (Recessive: OR = 1.43, 95% CI = 1.08-1.91, P = 0.013), and subgroup analysis also confirmed the relationship (English publications-recessive model: OR = 1.45, 95% CI = 1.10-1.91, P = 0.009; Studies in China-recessive model: OR = 1.58, 95% CI = 1.08-2.30, P = 0.017). No publication bias was detected. Conclusion: The meta-analysis indicated a significant inverse association between GG genotype carriage and elevated risk of gastric cancer. However, more studies and detailed information are needed to fully address the topic.