Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract

Xiu-Feng Huang,Lue Xiang,Wan Cheng,Fei-Fei Cheng,Kai-Wen He,Bo-Wen Zhang,Si-Si Zheng,Ru-Yi Han,Yi-Han Zheng,Xiao-Tao Xu,Huan-Yun Yu,Wenjuan Zhuang,Yuk Fai Leung,Zi-Bing Jin 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p. R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholinooligonucleotide- induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.

Prostate-specific Antigen Velocity (PSAV) and PSAV per Initial Volume (PSAVD) for Early Detection of Prostate Cancer in Chinese Men

Zheng, Xiang-Yi,Zhang, Peng,Xie, Li-Ping,You, Qi-Han,Cai, Bo-Sen,Qin, Jie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Aim: To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men. Methods: Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis. Results: Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0ng/mL-10.0ng was 73.7% and 70.7%, respectively. Conclusions: The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.

Assessing the Impact of Advanced Technologies on Utilization Improvement of Substations

Han, Dong,Yan, Zheng,Zhang, Dao-Tian,Song, Yi-Qun The Korean Institute of Electrical Engineers 2015 Journal of Electrical Engineering & Technology Vol.10 No.5

The smart substation is the heart of a transmission system, which is particularly emphasized as the most significant composition of smart grids in China. In order to assess the functionality performance of substation technologies, this paper presents methods used to identify the most promising solutions for smart substation design and to evaluate the technical levels of available technologies. The multi-index optimization model is presented to address the issue of smart substation planning. A mathematical model of the planning decision problem is established with multiple objectives consisting of economic, reliability, and green key indices, and many kinds of concerns including physical and environmentally friendly operations are formulated as a set of constraints. With respect to the assessment of the technical level regarding integration of advanced technologies into a substation, a modified grey whitenization weight function is adopted to structure a novel grey clustering method. The proposed grey clustering approach is used to overcome the difficulty of insufficient quantitative assessment capacity for traditional methods. The evaluation of technical effects provides the classification definition for the development phase and the maturity level of the smart substation. The effectiveness of the proposed approaches in planning decision-making and evaluation of construction efforts is demonstrated with case studies involving the actual smart substation projects of Wenchongkou substation in China Southern Power Grid (CSG) and Mengzi substation in State Grid Corporation of China (SGCC).

A Highly Active Alpha Amylase from Bacillus Licheniformis: Directed Evolution, Enzyme Characterization and Structural Analysis

( Yi Han Liu ),( Shu Ai Fan ),( Xiao Guang Liu ),( Zhi Meng Zhang ),( Jian Ling Wang ),( Zheng Xiang Wang ),( Fu Ping Lu ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.7

The stability of Bacillus licheniformis alpha-amylase (BLA) under acid condition was enhanced through direct evolution using the error-prone polymerase chain reaction. One beneficial mutation site, H281I, was obtained in BLA. The specific activity of H281I was 161/352 U/mg, which was 62.6/27.5% higher than that of the wild-type (WT) (99/276 U/mg) at pH 4.5/6.5 and 95°C. The pH optimum for H281I was decreased about 1 unit, whereas no significant changes of optimum temperature and thermostability were observed compared with the wild type (WT). The kcat/Km value of H281I was 1.7-/1.4-fold higher at pH 4.5/6.5, respectively, than that of WT. The structure model analysis indicated that the H281I mutation altered the predicted interaction between the amino acid residues at 281 and 273, thus creating a conducive local environment for substrate binding, as reflected by its decreased Km, and consequently increased the specific activity.

Development and validation of modified QuEChERS method coupled with LC–MS/MS for simultaneous determination of cymiazole, fipronil, coumaphos, fluvalinate, amitraz, and its metabolite in various types of honey and royal jelly

Zheng, Weijia,Park, Jin-A.,Abd El-Aty, A.M.,Kim, Seong-Kwan,Cho, Sang-Hyun,Choi, Jeong-min,Yi, Hee,Cho, Soo-Min,Ramadan, Amer,Jeong, Ji Hoon,Shim, Jae-Han,Shin, Ho-Chul Elsevier 2018 Journal of chromatography. B, Analytical technolog Vol.1072 No.-

<P><B>Abstract</B></P> <P>Over the past few decades, honey products have been polluted by different contaminants, such as pesticides, which are widely applied in agriculture. In this work, a modified EN – quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method was developed for the simultaneous quantification of pesticide residues, including cymiazole, fipronil, coumaphos, fluvalinate, amitraz, and its metabolite 2,4-dimethylaniline (2,4-DMA), in four types of honey (acacia, wild, chestnut, and manuka) and royal jelly. Samples were buffered with 0.2M dibasic sodium phosphate (pH 9), and subsequently, acetonitrile was employed as the extraction solvent. A combination of primary secondary amine (PSA) and C18 sorbents was used for purification prior to liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI<SUP>+</SUP>/MS-MS) analysis. The estimated linearity measured at six concentration levels presented good correlation coefficients (<I>R<SUP>2</SUP> </I>)≥0.99. The recovery, calculated from three different spiking levels, was 62.06–108.79% in honey and 67.58–106.34% in royal jelly, with an RSD<12% for all the tested compounds. The matrix effect was also evaluated, and most of the analytes presented signal enhancement. The limits of quantification (LOQ) ranged between 0.001 and 0.005mg/kg in various samples. These are considerably lower than the maximum residue limits (MRL) set by various regulatory authorities. A total of 43 market (domestic and imported) samples were assayed for method application. Among the tested samples, three samples were tested positive (i.e. detected and quantified) only for cymiazole residues. The residues in the rest of the samples were detected but not quantified. We concluded that the protocol developed in this work is simple and versatile for the routine quantification of cymiazole, 2,4-DMA, fipronil, coumaphos, amitraz, and fluvalinate in various types of honey and royal jelly.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Six pesticide residues in four types of honey and royal jelly were determined by LC–MS/MS analysis. </LI> <LI> Samples were extracted by a modified EN-QuEChERS method using both C18 sorbent and PSA. </LI> <LI> Recovery was good when the honey samples were extracted with 0.2M dibasic sodium phosphate buffer and acetonitrile. </LI> <LI> Three of the market samples tested positive for cymiazole residues. </LI> </UL> </P>

Bithionol residue analysis in animal-derived food products by an effective and rugged extraction method coupled with liquid chromatography–tandem mass spectrometry

Zheng, Weijia,Park, Jin-A,Abd El-Aty, A.M.,Kim, Seong-Kwan,Cho, Sang-Hyun,Choi, Jeong-Min,Yi, Hee,Cho, Soo-Min,El-Banna, H.A.,Shim, Jae-Han,Chang, Byung-Joon,Wang, Jing,Kim, Jin-Suk,Shin, Ho-Chul Elsevier 2017 Journal of chromatography. B, Analytical technolog Vol.1064 No.-

<P><B>Abstract</B></P> <P>Herein, we developed a simple analytical procedure for the quantitation of bithionol residues in animal-derived food products such as porcine muscle, eggs, milk, eel, flatfish, and shrimp using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI<SUP>+</SUP>/MS-MS). Samples were extracted with 0.1% solution of formic acid in acetonitrile and the extract was purified using a C18 sorbent. Separation was performed on a Waters XBridge™ C18 reversed-phase analytical column using 0.1% solution of formic acid/acetonitrile as the mobile phase. Six-point matrix-matched calibration indicated good linearity, with the calculated coefficients of determination (<I>R</I> <SUP>2</SUP>) being≥0.9813. Intra- and inter-day recoveries (determined at spiking levels equivalent to 1×and 2×the limit of quantitation (0.25μg/kg)) ranged between 80.0 and 94.0%, with the corresponding relative standard deviations (RSDs) being≤8.2%. The developed experimental protocol was applied to different samples purchased from local markets in Seoul, which were tested negative for bithionol residues. In conclusion, the proposed method proved to be versatile and precise, being ideally suited for the routine detection of bithionol residues in animal-derived food products with various protein and fat contents.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bithionol residues were quantified in porcine muscle, whole milk, eggs, eel, flatfish, and shrimp. </LI> <LI> Samples were extracted using a modified EN-QuEChERS method followed by LC–MS/MS analysis. </LI> <LI> Satisfactory extraction efficiency was obtained using 0.1% formic acid in acetonitrile as an extractant. </LI> <LI> None of the market samples tested positive for the target analyte. </LI> <LI> The developed method can help establish the MRL of bithionol, which is yet to be set by regulatory authorities. </LI> </UL> </P>

The role of extracellular vesicles in osteoarthritis treatment via microenvironment regulation

Han Yin,Muzhe Li,Guangzhao Tian,Yang Ma,Chao Ning,Zineng Yan,Jiang Wu,Qian Ge,Xiang Sui,Shu-Yun Liu,Jinxuan Zheng,Weimin Guo,Quan-Yi Guo 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Osteoarthritis (OA) is a degenerative joint disease that is common among the middle-aged and older populations, causes patients to experience recurrent pain in their joints and negatively affects their quality of life. Currently, therapeutic options for patients with OA consist of medications to alleviate pain and treat the symptoms; however, due to typically poor outcomes, patients with advanced OA are unlikely to avoid joint replacement. In recent years, several studies have linked disrupted homeostasis of the joint cavity microenvironment to the development of OA. Recently, extracellular vesicles (EVs) have received increasing attention in the field of OA. EVs are natural nano-microcarrier materials with unique biological activity that are produced by cells through paracrine action. They are composed of lipid bilayers that contain physiologically active molecules, such as nucleic acids and proteins. Moreover, EVs may participate in local and distal intercellular and intracellular communication. EVs have also recently been shown to influence OA development by regulating biochemical factors in the OA microenvironmental. In this article, we first describe the microenvironment of OA. Then, we provide an overview of EVs, summarize the main types used for the treatment of OA, and describe their mechanisms. Next, we review clinical studies using EVs for OA treatment. Finally, the specific mechanism underlying the application of miRNA-enriched EVs in OA therapy is described.

Different Catabolism Pathways Triggered by Various Methylxanthines in Caffeine-Tolerant Bacterium Pseudomonas putida CT25 Isolated from Tea Garden Soil

( Yi-xiao Ma ),( Xiao-han Wu ),( Hui-shi Wu ),( Zhan-bo Dong ),( Jian-hui Ye ),( Xin-qiang Zheng ),( Yue-rong Liang ),( Jian-liang Lu ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.7

The degradation efficiency and catabolism pathways of the different methylxanthines (MXs) in isolated caffeine-tolerant strain Pseudomonas putida CT25 were comprehensively studied. The results showed that the degradation efficiency of various MXs varied with the number and position of the methyl groups on the molecule (i.e., xanthine > 7-methylxanthine ≈ theobromine > caffeine > theophylline > 1-methylxanthine). Multiple MX catabolism pathways coexisted in strain CT25, and a different pathway would be triggered by various MXs. Demethylation dominated in the degradation of N-7-methylated MXs (such as 7- methylxanthine, theobromine, and caffeine), where C-8 oxidation was the major pathway in the catabolism of 1-methylxanthine, whereas demethylation and C-8 oxidation are likely both involved in the degradation of theophylline. Enzymes responsible for MX degradation were located inside the cell. Both cell culture and cell-free enzyme assays revealed that N-1 demethylation might be a rate-limiting step for the catabolism of the MXs. Surprisingly, accumulation of uric acid was observed in a cell-free reaction system, which might be attributed to the lack of activity of uricase, a cytochrome c-coupled membrane integral enzyme.

Assessing the Impact of Advanced Technologies on Utilization Improvement of Substations

Dong Han,Zheng Yan,Dao-Tian Zhang,Yi-Qun Song 대한전기학회 2015 Journal of Electrical Engineering & Technology Vol.10 No.5

The smart substation is the heart of a transmission system, which is particularly emphasized as the most significant composition of smart grids in China. In order to assess the functionality performance of substation technologies, this paper presents methods used to identify the most promising solutions for smart substation design and to evaluate the technical levels of available technologies. The multi-index optimization model is presented to address the issue of smart substation planning. A mathematical model of the planning decision problem is established with multiple objectives consisting of economic, reliability, and green key indices, and many kinds of concerns including physical and environmentally friendly operations are formulated as a set of constraints. With respect to the assessment of the technical level regarding integration of advanced technologies into a substation, a modified grey whitenization weight function is adopted to structure a novel grey clustering method. The proposed grey clustering approach is used to overcome the difficulty of insufficient quantitative assessment capacity for traditional methods. The evaluation of technical effects provides the classification definition for the development phase and the maturity level of the smart substation. The effectiveness of the proposed approaches in planning decision-making and evaluation of construction efforts is demonstrated with case studies involving the actual smart substation projects of Wenchongkou substation in China Southern Power Grid (CSG) and Mengzi substation in State Grid Corporation of China (SGCC).

The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease

Cheng Han Ng,Kai En Chan,Yip Han Chin,Rebecca Wenling Zeng,Pei Chen Tsai,Wen Hui Lim,Darren Jun Hao Tan,Chin Meng Khoo,Lay Hoon Goh,Zheng Jye Ling,Anand Kulkarni,Lung-Yi Loey Mak,Daniel Q Huang,Mark C 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods: Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions: Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.