This study employed a simulated an-nealing algorithm to develop new re-active force field(ReaxFF)parame-ters specifically tailored for thiol oxi-dation and disulfide cross-linking re-actions.The optimization strategy ...This study employed a simulated an-nealing algorithm to develop new re-active force field(ReaxFF)parame-ters specifically tailored for thiol oxi-dation and disulfide cross-linking re-actions.The optimization strategy demonstrably enhanced the capabili-ty of ReaxFF to model these chemi-cal processes.To mitigate potential overfitting during parameterization,we strategically expanded the training set’s conformational space relevant to the reactions through normal mode analysis.This approach effectively addressed concerns about overfit-ting,and the resulting parameters exhibit a degree of scalability for similar reactions.The op-timized parameters achieve good agreement with experimental reaction energies.While sur-passing the original parameters in accuracy,the characterization of reaction energy barriers is not ideal due to the exclusion of parameters related to O-H bond during optimization and in-herent limitations within the ReaxFF framework.However,the current level of accuracy is sufficient for preliminary semi-quantitative studies.Notably,molecular dynamics simulations utilizing the new parameters successfully captured the binding mode of reactants in solvent-mediated proton transfer reactions,even for systems beyond the training set.These advance-ments in the ReaxFF force field offer a more efficient and reliable computational tool for ex-ploring thiol oxidation and disulfide cross-linking reactions relevant to biological systems.展开更多
Oxidative stress, the imbalance between the production of reactive oxygen species （ROS） and antioxidant activity is a major culprit of male infertility. Peroxiredoxins （PRDXs） are major antioxidant enzymes of mamm...Oxidative stress, the imbalance between the production of reactive oxygen species （ROS） and antioxidant activity is a major culprit of male infertility. Peroxiredoxins （PRDXs） are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide （tert-BHP） treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 -moles tert-BHP/kg or saline （control） per day intraperitoneal for 15 days. Lipid peroxidation （2-thibarbituric acid reactive substances assay）, total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase （SOD）, motility and DNA oxidation （8-hydroxy-deoxyguanosine） were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs （and not SOD） amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation.展开更多
AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy vo...AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol(P = 0.027) and total thiol(P = 0.031) levels were lower, while disulphide(P < 0.001) level, disulphide/native thiol(P < 0.001) and disulphide/total thiol(P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet(P < 0.001). In patients withany autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative(P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels.CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group.展开更多
An efficient and convenient tert-butyl nitrite-catalyzed selective aerobic oxidation of thiols has been developed. Under the optimal reaction conditions, a number of thiol derivatives including aromatic thiols, hetero...An efficient and convenient tert-butyl nitrite-catalyzed selective aerobic oxidation of thiols has been developed. Under the optimal reaction conditions, a number of thiol derivatives including aromatic thiols, heteroaromatic thiols and aliphatic thiols can be converted into their corresponding disulfides in good to excellent yields.展开更多
文摘This study employed a simulated an-nealing algorithm to develop new re-active force field(ReaxFF)parame-ters specifically tailored for thiol oxi-dation and disulfide cross-linking re-actions.The optimization strategy demonstrably enhanced the capabili-ty of ReaxFF to model these chemi-cal processes.To mitigate potential overfitting during parameterization,we strategically expanded the training set’s conformational space relevant to the reactions through normal mode analysis.This approach effectively addressed concerns about overfit-ting,and the resulting parameters exhibit a degree of scalability for similar reactions.The op-timized parameters achieve good agreement with experimental reaction energies.While sur-passing the original parameters in accuracy,the characterization of reaction energy barriers is not ideal due to the exclusion of parameters related to O-H bond during optimization and in-herent limitations within the ReaxFF framework.However,the current level of accuracy is sufficient for preliminary semi-quantitative studies.Notably,molecular dynamics simulations utilizing the new parameters successfully captured the binding mode of reactants in solvent-mediated proton transfer reactions,even for systems beyond the training set.These advance-ments in the ReaxFF force field offer a more efficient and reliable computational tool for ex-ploring thiol oxidation and disulfide cross-linking reactions relevant to biological systems.
文摘Oxidative stress, the imbalance between the production of reactive oxygen species （ROS） and antioxidant activity is a major culprit of male infertility. Peroxiredoxins （PRDXs） are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide （tert-BHP） treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 -moles tert-BHP/kg or saline （control） per day intraperitoneal for 15 days. Lipid peroxidation （2-thibarbituric acid reactive substances assay）, total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase （SOD）, motility and DNA oxidation （8-hydroxy-deoxyguanosine） were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs （and not SOD） amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation.
文摘AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol(P = 0.027) and total thiol(P = 0.031) levels were lower, while disulphide(P < 0.001) level, disulphide/native thiol(P < 0.001) and disulphide/total thiol(P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet(P < 0.001). In patients withany autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative(P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels.CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group.
基金financially supported by the National Natural Science Foundation of China (Nos. 21376224, 21206147)
文摘An efficient and convenient tert-butyl nitrite-catalyzed selective aerobic oxidation of thiols has been developed. Under the optimal reaction conditions, a number of thiol derivatives including aromatic thiols, heteroaromatic thiols and aliphatic thiols can be converted into their corresponding disulfides in good to excellent yields.
