Reactive oxygen species(ROS)play a key role in a variety of biological processes,such as the perception of abiotic stress,the integration of different environmental signals,and the activation of stress response networ...Reactive oxygen species(ROS)play a key role in a variety of biological processes,such as the perception of abiotic stress,the integration of different environmental signals,and the activation of stress response networks.Salt stress could induce an increased ROS accumulation in plants,disrupting intracellular redox homeostasis,leading to posttranslational modifications(PTMs)of specific proteins,and eventually causing adaptive changes in metabolism.Here,we performed an iodoTMT-based proteomic approach to identify the sulfenylated proteins in B.napus root responsing to salt stress.Totally,1348 sulfenylated sites in 751 proteins were identified and these proteins were widely existed in different cell compartments and processes.Our study revealed that proteins with changed abundance and sulfenylation level in B.napus root under salt stress were mainly enriched in the biological processes of ion binding,glycolysis,ATP binding,and oxidative stress response.This study displays a landscape of sulfenylated proteins response to salt stress in B.napus root and provides some theoretical support for further understanding of the molecular mechanisms of redox regulation under salt stress in plants.展开更多
E3 ubiquitin ligases catalyze the final step of ubiquitylation,a crucial post-translational modification involved in almost every process in eukaryotic cells.E3 ubiquitin ligases are key regulators of cellular events,...E3 ubiquitin ligases catalyze the final step of ubiquitylation,a crucial post-translational modification involved in almost every process in eukaryotic cells.E3 ubiquitin ligases are key regulators of cellular events,and the investigation into their functions and functioning mechanisms are research areas with great importance.Synthetic or semi-synthetic tools have greatly facilitated the research about the enzyme activity,distribution in different physiological events,and catalytic mechanism of E3 ubiquitin ligase.In this review,we summarize the development of chemical tools for E3 ubiquitin ligases with an emphasis on the synthetic routes.We show the utility of these chemical tools by briefly discussing their applications in biological research.展开更多
Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by usi...Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure.展开更多
NES1 gene is thought to be a tumor-suppressor gene.Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate,associated with a mild decrease in BCL-2 expre...NES1 gene is thought to be a tumor-suppressor gene.Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate,associated with a mild decrease in BCL-2 expression.The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors.Thus,we supposed to have an“enhanced firepower”effect by combining overexpressed NES1 gene therapy and 131I radiation therapy uptake by overexpressed hNIS protein.We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake.By overexpressing hNIS in PC3,the radioactive iodine uptake ability was significantly increased.Results of in vitro and in vivo tumor proliferation experiments and 18F-fluorothymidine(18F-FLT)micro-positron emission tomography/computed tomography(micro-PET/CT)imaging showed that the combined NES1 gene therapy and 131I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect.Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression.These data suggest that via inhibition of BCL-2 expression,overexpressed NES1 might enhance the effect of radiation therapy of 131I uptake in hNIS overexpressed PC3 cells.展开更多
In this work, a kind of preparation method of zwitterionic ion chromatography (ZIC) stationary phase modified with phosphorylcholine (PC) was obtained by hydrolyzing after bonding phosphorylcholine dichloride to d...In this work, a kind of preparation method of zwitterionic ion chromatography (ZIC) stationary phase modified with phosphorylcholine (PC) was obtained by hydrolyzing after bonding phosphorylcholine dichloride to diol-silica to better explore the characteristics of the PC groups as ZIC stationary phase ligand in simultaneous separation of acidic proteins and basic proteins. The results showed that tv^o kinds of acidic proteins and three kinds of basic proteins can be separated completely, meanwhile, hen egg white was separated and purified and three kinds of egg white components ovalbumin, G2 ovoglobulin and ovotransfemin proteins were separated completely by one single step on PC-ZIC column, the purity of all proteins reached above 95%. PC-ZIC stationary phase was successfully improved with better separation capacity and selectivity than previously reported in this paper.展开更多
Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FD...Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation(IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds.展开更多
An effective broad-spectrum fungicide,azoxystrobin(AZ),has been widely detected in aquatic ecosystems,potentially affecting the growth of aquatic microorganisms.In the present study,the eukaryotic alga Monoraphidium s...An effective broad-spectrum fungicide,azoxystrobin(AZ),has been widely detected in aquatic ecosystems,potentially affecting the growth of aquatic microorganisms.In the present study,the eukaryotic alga Monoraphidium sp.and the cyanobacterium Pseudanabaena sp.were exposed to AZ for 7 days.Our results showed that 0.2–0.5 mg/L concentrations of AZ slightly inhibited the growth of Monoraphidium sp.but stimulated Pseudanabaena sp.growth.Meanwhile,AZ treatment effectively increased the secretion of total organic carbon(TOC)in the culture media of the two species,and this phenomenon was also found in a freshwater microcosm experiment(containing the natural microbial community).We attempted to assess the effect of AZ on the function of aquatic microbial communities through metabolomic analysis and further explore the potential risks of this compound.The metabonomic profiles of the microcosm indicated that the most varied metabolites after AZ treatment were related to the citrate cycle(TCA),fatty acid biosynthesis and purine metabolism.We thereby inferred that the microbial community increased extracellular secretions by adjusting metabolic pathways,which might be a stress response to reduce AZ toxicity.Our results provide an important theoretical basis for further study of fungicide stress responses in aquatic microcosm microbial communities,as well as a good start for further explorations of AZ detoxification mechanisms,which will be valuable for the evaluation of AZ environmental risk.展开更多
Imazethapyr(IM)is a widely used acetolactate synthase-inhibiting chiral herbicide.It has long-term residuals that may be absorbed by the human body through the edible parts of plants,such as vegetable leaves or fruits...Imazethapyr(IM)is a widely used acetolactate synthase-inhibiting chiral herbicide.It has long-term residuals that may be absorbed by the human body through the edible parts of plants,such as vegetable leaves or fruits.Here,we selected a model plant,Arabidopsis thaliana,to determine the effects of R-IM and S-IM on its leaf structure,photosynthetic efficiency,and metabolites,as well as the structures of microorganisms in the phyllosphere,after 7 days of exposure.Our results indicated enantiomeric differences in plant growth between R-IM and S-IM;133μg/kg R-IM showed heavier inhibition of photosynthetic efficiency and greater changes to subcellular structure than S-IM.R-IM and S-IM also had different effects on metabolism and leaf microorganisms.S-IM mainly increased lipid compounds and decreased amino acids,while R-IM increased sugar accumulation.The relative abundance of Moraxellaceae human pathogenic bacteria was increased by R-IM treatment,indicating that R-IM treatment may increase leaf surface pathogenic bacteria.Our research provides a new perspective for evaluating the harmfulness of pesticide residues in soil,phyllosphere microbiome changes via the regulation of plant metabolism,and induced pathogenic bacterial accumulation risks.展开更多
Aim: To explore the characteristics of normal hair distribution in Han Chinese. Methods:A total of 146 healthy Han Chinese and 41 patients with androgenetic alopecia (AGA) were selected as research subjects. Digital p...Aim: To explore the characteristics of normal hair distribution in Han Chinese. Methods:A total of 146 healthy Han Chinese and 41 patients with androgenetic alopecia (AGA) were selected as research subjects. Digital photographs of the vertex, temporal, and occipital regions were taken after their hair was trimmed. An image analysis software was used to compute the number of follicular units (FUs) and hairs. Results: The mean FU density of the 146 healthy Han Chinese was 74.36 ± 13.33 units/cm2 and their mean hair density was 143.33 ± 28.08 hairs/cm2. There was no significant difference between males and females (P >0.05). The mean FU density in the occipital region of AGA patients was 77.78 ± 2.99 units/cm2 and their mean hair count was 148.12 ± 6.98 hairs/cm2. Both were lower than those of healthy Han Chinese, and the differences were statistically significant (P < 0.001). Two-hair FUs (52.62%) were the predominant type found in Han Chinese. Conclusion: The FU and hair densities of healthy Han Chinese are lower than those of whites and Africans. The study provides hair transplantation surgeons with information on hair distribution in Han Chinese. It also provides a quantitative basis for the area of donor site and transplantation density necessary for hair transplantation surgeries. The research findings provide some theoretical data for the hair distribution characteristics of Han Chinese. These data can contribute to the preoperative assessment, surgery planning, and postoperative outcome evaluation by hair transplantation surgeons.展开更多
基金funded by the Major Scientific and Technological Projects of Xinjiang Production and Construction Corps of China[2018AA005]and the 111 Project[B20051]supported by the PTM Biolabs lnc.[Hangzhou,China]for technical assistance.
文摘Reactive oxygen species(ROS)play a key role in a variety of biological processes,such as the perception of abiotic stress,the integration of different environmental signals,and the activation of stress response networks.Salt stress could induce an increased ROS accumulation in plants,disrupting intracellular redox homeostasis,leading to posttranslational modifications(PTMs)of specific proteins,and eventually causing adaptive changes in metabolism.Here,we performed an iodoTMT-based proteomic approach to identify the sulfenylated proteins in B.napus root responsing to salt stress.Totally,1348 sulfenylated sites in 751 proteins were identified and these proteins were widely existed in different cell compartments and processes.Our study revealed that proteins with changed abundance and sulfenylation level in B.napus root under salt stress were mainly enriched in the biological processes of ion binding,glycolysis,ATP binding,and oxidative stress response.This study displays a landscape of sulfenylated proteins response to salt stress in B.napus root and provides some theoretical support for further understanding of the molecular mechanisms of redox regulation under salt stress in plants.
文摘E3 ubiquitin ligases catalyze the final step of ubiquitylation,a crucial post-translational modification involved in almost every process in eukaryotic cells.E3 ubiquitin ligases are key regulators of cellular events,and the investigation into their functions and functioning mechanisms are research areas with great importance.Synthetic or semi-synthetic tools have greatly facilitated the research about the enzyme activity,distribution in different physiological events,and catalytic mechanism of E3 ubiquitin ligase.In this review,we summarize the development of chemical tools for E3 ubiquitin ligases with an emphasis on the synthetic routes.We show the utility of these chemical tools by briefly discussing their applications in biological research.
基金We thank the National Key R&D Program of China(2017YFA0505200,2016YFA0400903,and 2015CB910103)National Science Foundation of China(91753205,21532004,21761142008,81621002,21621003,91849129,and 21708036)for their financial support.
文摘Mutations in genes encoding PINK1(PTEN-induced kinase 1)and Parkin(E3 ubiquitin ligase)are identified in familial Parkinson’s disease.However,it remains unclear whether the phosphorylated Ub chains activate wild-type Parkin(w-Parkin)or phosphorylated Parkin(p-Parkin),with the consequent expulsion of the damaged mitochondria.
基金supported by the National Natural Science Foundation of China (21572043, 21473176)the Ministry of Science and Technology (2016YFA0400900, 2015CB910103)the Fundamental Research Funds for the Central Universities (PA2017GDQT0021)
文摘Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure.
文摘NES1 gene is thought to be a tumor-suppressor gene.Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate,associated with a mild decrease in BCL-2 expression.The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors.Thus,we supposed to have an“enhanced firepower”effect by combining overexpressed NES1 gene therapy and 131I radiation therapy uptake by overexpressed hNIS protein.We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake.By overexpressing hNIS in PC3,the radioactive iodine uptake ability was significantly increased.Results of in vitro and in vivo tumor proliferation experiments and 18F-fluorothymidine(18F-FLT)micro-positron emission tomography/computed tomography(micro-PET/CT)imaging showed that the combined NES1 gene therapy and 131I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect.Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression.These data suggest that via inhibition of BCL-2 expression,overexpressed NES1 might enhance the effect of radiation therapy of 131I uptake in hNIS overexpressed PC3 cells.
基金supported by the National Natural Science Foundation(No.21006077)the foundation of science and technology in Shaanxi Province(No.2010K12-01-05)the foundation for construction of key disciplines of analytical chemistry in Shaanxi Province
文摘In this work, a kind of preparation method of zwitterionic ion chromatography (ZIC) stationary phase modified with phosphorylcholine (PC) was obtained by hydrolyzing after bonding phosphorylcholine dichloride to diol-silica to better explore the characteristics of the PC groups as ZIC stationary phase ligand in simultaneous separation of acidic proteins and basic proteins. The results showed that tv^o kinds of acidic proteins and three kinds of basic proteins can be separated completely, meanwhile, hen egg white was separated and purified and three kinds of egg white components ovalbumin, G2 ovoglobulin and ovotransfemin proteins were separated completely by one single step on PC-ZIC column, the purity of all proteins reached above 95%. PC-ZIC stationary phase was successfully improved with better separation capacity and selectivity than previously reported in this paper.
基金supported by the National Natural Science Foundation of China (NSFC No. 21572043)the Fundamental Research Funds for the Central Universities (No. PA2017GDQT0021)
文摘Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation(IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds.
基金supported by the National Key Research and Development Program of China(No.2017YFD0200503)the National Natural Science Foundation of China(Nos.21777144,21976161)the Changjiang Scholars and Innovative Re-search Team in University(No.IRT_17R97)。
文摘An effective broad-spectrum fungicide,azoxystrobin(AZ),has been widely detected in aquatic ecosystems,potentially affecting the growth of aquatic microorganisms.In the present study,the eukaryotic alga Monoraphidium sp.and the cyanobacterium Pseudanabaena sp.were exposed to AZ for 7 days.Our results showed that 0.2–0.5 mg/L concentrations of AZ slightly inhibited the growth of Monoraphidium sp.but stimulated Pseudanabaena sp.growth.Meanwhile,AZ treatment effectively increased the secretion of total organic carbon(TOC)in the culture media of the two species,and this phenomenon was also found in a freshwater microcosm experiment(containing the natural microbial community).We attempted to assess the effect of AZ on the function of aquatic microbial communities through metabolomic analysis and further explore the potential risks of this compound.The metabonomic profiles of the microcosm indicated that the most varied metabolites after AZ treatment were related to the citrate cycle(TCA),fatty acid biosynthesis and purine metabolism.We thereby inferred that the microbial community increased extracellular secretions by adjusting metabolic pathways,which might be a stress response to reduce AZ toxicity.Our results provide an important theoretical basis for further study of fungicide stress responses in aquatic microcosm microbial communities,as well as a good start for further explorations of AZ detoxification mechanisms,which will be valuable for the evaluation of AZ environmental risk.
基金supported by the National Natural Science Foundation of China(Nos.21777144,21976161)the CAS Pioneer Hundred Talents Program(H.F.Qian)the Xinjiang Uighur Autonomous Region Talent Project(H.F.Qian)。
文摘Imazethapyr(IM)is a widely used acetolactate synthase-inhibiting chiral herbicide.It has long-term residuals that may be absorbed by the human body through the edible parts of plants,such as vegetable leaves or fruits.Here,we selected a model plant,Arabidopsis thaliana,to determine the effects of R-IM and S-IM on its leaf structure,photosynthetic efficiency,and metabolites,as well as the structures of microorganisms in the phyllosphere,after 7 days of exposure.Our results indicated enantiomeric differences in plant growth between R-IM and S-IM;133μg/kg R-IM showed heavier inhibition of photosynthetic efficiency and greater changes to subcellular structure than S-IM.R-IM and S-IM also had different effects on metabolism and leaf microorganisms.S-IM mainly increased lipid compounds and decreased amino acids,while R-IM increased sugar accumulation.The relative abundance of Moraxellaceae human pathogenic bacteria was increased by R-IM treatment,indicating that R-IM treatment may increase leaf surface pathogenic bacteria.Our research provides a new perspective for evaluating the harmfulness of pesticide residues in soil,phyllosphere microbiome changes via the regulation of plant metabolism,and induced pathogenic bacterial accumulation risks.
基金the Natural Science Foundation of China(81471900)the Natural Science Foundation of China(81772104)+2 种基金Natural Science Foundation of China(81701929)Natural Science Foundation of Guangdong Province(2015A030311001)Science and Technology Program of Guangzhou(201508020262).
文摘Aim: To explore the characteristics of normal hair distribution in Han Chinese. Methods:A total of 146 healthy Han Chinese and 41 patients with androgenetic alopecia (AGA) were selected as research subjects. Digital photographs of the vertex, temporal, and occipital regions were taken after their hair was trimmed. An image analysis software was used to compute the number of follicular units (FUs) and hairs. Results: The mean FU density of the 146 healthy Han Chinese was 74.36 ± 13.33 units/cm2 and their mean hair density was 143.33 ± 28.08 hairs/cm2. There was no significant difference between males and females (P >0.05). The mean FU density in the occipital region of AGA patients was 77.78 ± 2.99 units/cm2 and their mean hair count was 148.12 ± 6.98 hairs/cm2. Both were lower than those of healthy Han Chinese, and the differences were statistically significant (P < 0.001). Two-hair FUs (52.62%) were the predominant type found in Han Chinese. Conclusion: The FU and hair densities of healthy Han Chinese are lower than those of whites and Africans. The study provides hair transplantation surgeons with information on hair distribution in Han Chinese. It also provides a quantitative basis for the area of donor site and transplantation density necessary for hair transplantation surgeries. The research findings provide some theoretical data for the hair distribution characteristics of Han Chinese. These data can contribute to the preoperative assessment, surgery planning, and postoperative outcome evaluation by hair transplantation surgeons.