A 26-year-old patient with mirror-image dextrocardia and situs inversus experienced a transient ischemic attack.We suspected that a patent foramen ovale was the reason.A Cardi-O-Fix occluder was used to close the pate...A 26-year-old patient with mirror-image dextrocardia and situs inversus experienced a transient ischemic attack.We suspected that a patent foramen ovale was the reason.A Cardi-O-Fix occluder was used to close the patent foramen ovale with a mirror-reversed rotation of the radiologic views.During the 18-month follow-up,no symptoms of the transient ischemic attack appeared again.展开更多
Straightforward techniques for spatial domain digital video editing (DVE) of compressed video via decompression and recompression are computationally expensive. In this paper, a novel algorithm was proposed for mirror...Straightforward techniques for spatial domain digital video editing (DVE) of compressed video via decompression and recompression are computationally expensive. In this paper, a novel algorithm was proposed for mirror-image special effect editing in compressed video without full frame decompression and motion estimation. The results show that with the reducing of computational complexity, the quality of edited video in compressed domain is still close to the quality of the edited video in uncompressed domain at the same bit rate.展开更多
Objective:To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.Methods:A total of 48 adult male Sprague-...Objective:To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.Methods:A total of 48 adult male Sprague-Dawley rats(weighing 180 g-220 g)were included in the study and randomized into 3 groups,Group S,Group R,and Group RD,.A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups.Before procedures and nerve extraction,Group S(n=16)was injected 0.9%saline locally;Group R(n=16)was injected 0.5%ropivocaine locally,and Group RD,(n=16)was injected 0.5%ropivocaine in combined with 1μg dexmedetomidine locally.After the model being established in the three groups,8 rats were used for behavior test until 28 d,and dorsal root ganglions(DRGs)of the other 8 rats were harvested on the3 rd day after surgery.Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG,and the behavior test results in the three groups were compared.Results:The results showed that mechanical pain threshold in ipsilateral hindpaws of the Group S,Group R,Group RD,animals dropped to(3.640±1.963)g,(5.827±1.204)g,(7.482)±1.412 g at 3 d respectively;while in contralateral paws dropped to(7.100±1.789)g,(17.687±1.112)g,(16.213±1.345)g on the 3 d respectively.Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups,but ipsilateral paws expressed more active glial cells than contralateral paws.Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws,but Group RD,formula could reduce glial cells activity,mitochondria swelling/vacuolization and the amount of lysosomes.Conclusions:Local injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG,mitigate the pathological changes of neuron in DRG and reduce mirror image pain.展开更多
A mirror-image protein-based information barcoding and storage technology wherein D-amino acids are used to encode information into mirror-image proteins that are chemically synthesized is described.These mirror-image...A mirror-image protein-based information barcoding and storage technology wherein D-amino acids are used to encode information into mirror-image proteins that are chemically synthesized is described.These mirror-image proteins were then fused into various materials from which information-encoded objects were produced.Subsequently,the mirror-image proteins were extracted from the objects using biotin-streptavidin resin-mediated specific enrichment and cleaved using an Ni(Ⅱ)-mediated selective peptide cleavage.Protein sequencing was accomplished using liquid chromatography/tandem mass spectrometry(LC-MS/MS)and then transcoded into the recorded information.We demonstrated the use of this technology to encode Chinese words into mirror-image proteins,which were then fused onto a poly(ethylene terephthalate)(PET)film and retrieved and decoded by LC-MS/MS sequencing.Compared to information barcoding and storage technologies using natural biopolymers,the mirrorimage biopolymers used in our technology may be more stable and durable.展开更多
Wide Sargasso Sea,from the perspective of the woman in the attic,tells the story that is covered in the Jane Eyre.This article mainly focuses on the depriving of speaking right,three relationships of Bertha with other...Wide Sargasso Sea,from the perspective of the woman in the attic,tells the story that is covered in the Jane Eyre.This article mainly focuses on the depriving of speaking right,three relationships of Bertha with others and her dream,which all reflect her identity crisis in her life.展开更多
The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemi...The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.展开更多
D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and spe...D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery.展开更多
In the rapidly expanding field of peptide therapeutics,the short in vivo half-life of peptides represents a considerable limitation for drug action.D-peptides,consisting entirely of the dextrorotatory enantiomers of n...In the rapidly expanding field of peptide therapeutics,the short in vivo half-life of peptides represents a considerable limitation for drug action.D-peptides,consisting entirely of the dextrorotatory enantiomers of naturally occurring levorotatory amino acids(AAs),do not suffer from these shortcomings as they are intrinsically resistant to proteolytic degradation,resulting in a favourable pharmacokinetic profile.To experimentally identify D-peptide binders to interesting therapeutic targets,so-called mirror-image phage display is typically performed,whereby the target is synthesized in D-form and L-peptide binders are screened as in conventional phage display.This technique is extremely powerful,but it requires the synthesis of the target in D-form,which is challenging for large proteins.Here we present finDr,a novel web server for the computational identification and optimization of D-peptide ligands to any protein structure(https://findr.biologie.uni-freiburg.de/).finDr performs molecular docking to virtually screen a library of helical 12-mer peptides extracted from the RCSB Protein Data Bank(PDB)for their ability to bind to the target.In a separate,heuristic approach to search the chemical space of 12-mer peptides,finDr executes a customizable evolutionary algorithm(EA)for the de novo identification or optimization of D-peptide ligands.As a proof of principle,we demonstrate the validity of our approach to predict optimal binders to the pharmacologically relevant target phenol soluble modulin alpha 3(PSMα3),a toxin of methicillin-resistant Staphylococcus aureus(MRSA).We validate the predictions using in vitro binding assays,supporting the success of this approach.Compared to conventional methods,finDr provides a low cost and easy-to-use alternative for the identification of D-peptide ligands against protein targets of choice without size limitation.We believe finDr will facilitate D-peptide discovery with implications in biotechnology and biomedicine.展开更多
In this paper the analytical expressions for the magnetic field H and induction B in iron-pole plates generated by MRI gradient coil are given using line-current and the multilayer dielectric plate model with the mirr...In this paper the analytical expressions for the magnetic field H and induction B in iron-pole plates generated by MRI gradient coil are given using line-current and the multilayer dielectric plate model with the mirror-image method.Eddy current emanates from the magnetic flux in the iron-pole plates.In order to fully suppress the eddy current,this magnetic flux should be fully eliminated.The research results indicate the magnetic permeability of the resist-eddy plate must be bigger than that of magnetic pole material,i.e.pure iron,and that the resist-eddy plate should be thick enough to be far away from its magnetic saturation.展开更多
Interleukin 5(IL-5) is a human cytokine that regulates eosinophil growth and activation, and it plays essential roles in diseases associated with increased level of eosinophils such as asthma. Many studies have been c...Interleukin 5(IL-5) is a human cytokine that regulates eosinophil growth and activation, and it plays essential roles in diseases associated with increased level of eosinophils such as asthma. Many studies have been conducted on this important glycoprotein, but all of them utilized recombinantly expressed samples. Here we describe our attempted chemical synthesis of IL-5, using protocols of Fmoc-SPPS and peptidyl hydrazide-based native chemical ligation, where the disulfide-reduced form of IL-5 is assembled from three peptide segments. Reconstitution of the protein under different folding conditions has also been investigated.展开更多
文摘A 26-year-old patient with mirror-image dextrocardia and situs inversus experienced a transient ischemic attack.We suspected that a patent foramen ovale was the reason.A Cardi-O-Fix occluder was used to close the patent foramen ovale with a mirror-reversed rotation of the radiologic views.During the 18-month follow-up,no symptoms of the transient ischemic attack appeared again.
文摘Straightforward techniques for spatial domain digital video editing (DVE) of compressed video via decompression and recompression are computationally expensive. In this paper, a novel algorithm was proposed for mirror-image special effect editing in compressed video without full frame decompression and motion estimation. The results show that with the reducing of computational complexity, the quality of edited video in compressed domain is still close to the quality of the edited video in uncompressed domain at the same bit rate.
基金supported by the Natural Science Foundation of China(NSFC)(Grant No.81100817)
文摘Objective:To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.Methods:A total of 48 adult male Sprague-Dawley rats(weighing 180 g-220 g)were included in the study and randomized into 3 groups,Group S,Group R,and Group RD,.A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups.Before procedures and nerve extraction,Group S(n=16)was injected 0.9%saline locally;Group R(n=16)was injected 0.5%ropivocaine locally,and Group RD,(n=16)was injected 0.5%ropivocaine in combined with 1μg dexmedetomidine locally.After the model being established in the three groups,8 rats were used for behavior test until 28 d,and dorsal root ganglions(DRGs)of the other 8 rats were harvested on the3 rd day after surgery.Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG,and the behavior test results in the three groups were compared.Results:The results showed that mechanical pain threshold in ipsilateral hindpaws of the Group S,Group R,Group RD,animals dropped to(3.640±1.963)g,(5.827±1.204)g,(7.482)±1.412 g at 3 d respectively;while in contralateral paws dropped to(7.100±1.789)g,(17.687±1.112)g,(16.213±1.345)g on the 3 d respectively.Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups,but ipsilateral paws expressed more active glial cells than contralateral paws.Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws,but Group RD,formula could reduce glial cells activity,mitochondria swelling/vacuolization and the amount of lysosomes.Conclusions:Local injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG,mitigate the pathological changes of neuron in DRG and reduce mirror image pain.
基金the National Key R&D Program of China(2017YFA0505200 and 2019YFA0706902)the National Natural Science Foundation of China(22022703,91753205,and 21750005)the Science and Technological Fund of Anhui Province for Outstanding Youth(1808085J04)。
文摘A mirror-image protein-based information barcoding and storage technology wherein D-amino acids are used to encode information into mirror-image proteins that are chemically synthesized is described.These mirror-image proteins were then fused into various materials from which information-encoded objects were produced.Subsequently,the mirror-image proteins were extracted from the objects using biotin-streptavidin resin-mediated specific enrichment and cleaved using an Ni(Ⅱ)-mediated selective peptide cleavage.Protein sequencing was accomplished using liquid chromatography/tandem mass spectrometry(LC-MS/MS)and then transcoded into the recorded information.We demonstrated the use of this technology to encode Chinese words into mirror-image proteins,which were then fused onto a poly(ethylene terephthalate)(PET)film and retrieved and decoded by LC-MS/MS sequencing.Compared to information barcoding and storage technologies using natural biopolymers,the mirrorimage biopolymers used in our technology may be more stable and durable.
文摘Wide Sargasso Sea,from the perspective of the woman in the attic,tells the story that is covered in the Jane Eyre.This article mainly focuses on the depriving of speaking right,three relationships of Bertha with others and her dream,which all reflect her identity crisis in her life.
基金supported by the National Key R&D Program of China(2022YFC3401500)the National Natural Science Foundation of China(22137005,92253302,22227810 to Lei Liu,22177004,92153301,22321005 to Suwei Dong,22277020 to Yiming Li,22022703,22177108,22377118 to Ji-Shen Zheng,92353302,22177059 to Yongxiang Chen,22177035 to Jun Guo,22277029,22077036 to Chunmao He,22077078 to Honggang Hu92353302,92053108 to Yanmei Li,22277015 to Junfeng Zhao)。
文摘The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.
基金supported by the National Key R&D Program of China(No.2019YFA0706902)National Natural Science Foundation of China(Nos.U1732161 and 91753120)Science and Technological Fund of Anhui Province for Outstanding Youth(No.1808085J04)。
文摘D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery.
文摘In the rapidly expanding field of peptide therapeutics,the short in vivo half-life of peptides represents a considerable limitation for drug action.D-peptides,consisting entirely of the dextrorotatory enantiomers of naturally occurring levorotatory amino acids(AAs),do not suffer from these shortcomings as they are intrinsically resistant to proteolytic degradation,resulting in a favourable pharmacokinetic profile.To experimentally identify D-peptide binders to interesting therapeutic targets,so-called mirror-image phage display is typically performed,whereby the target is synthesized in D-form and L-peptide binders are screened as in conventional phage display.This technique is extremely powerful,but it requires the synthesis of the target in D-form,which is challenging for large proteins.Here we present finDr,a novel web server for the computational identification and optimization of D-peptide ligands to any protein structure(https://findr.biologie.uni-freiburg.de/).finDr performs molecular docking to virtually screen a library of helical 12-mer peptides extracted from the RCSB Protein Data Bank(PDB)for their ability to bind to the target.In a separate,heuristic approach to search the chemical space of 12-mer peptides,finDr executes a customizable evolutionary algorithm(EA)for the de novo identification or optimization of D-peptide ligands.As a proof of principle,we demonstrate the validity of our approach to predict optimal binders to the pharmacologically relevant target phenol soluble modulin alpha 3(PSMα3),a toxin of methicillin-resistant Staphylococcus aureus(MRSA).We validate the predictions using in vitro binding assays,supporting the success of this approach.Compared to conventional methods,finDr provides a low cost and easy-to-use alternative for the identification of D-peptide ligands against protein targets of choice without size limitation.We believe finDr will facilitate D-peptide discovery with implications in biotechnology and biomedicine.
基金supported by the National Natural Science Foundation of China (Grant No 60871001)
文摘In this paper the analytical expressions for the magnetic field H and induction B in iron-pole plates generated by MRI gradient coil are given using line-current and the multilayer dielectric plate model with the mirror-image method.Eddy current emanates from the magnetic flux in the iron-pole plates.In order to fully suppress the eddy current,this magnetic flux should be fully eliminated.The research results indicate the magnetic permeability of the resist-eddy plate must be bigger than that of magnetic pole material,i.e.pure iron,and that the resist-eddy plate should be thick enough to be far away from its magnetic saturation.
基金financial support from the National Recruitment Program of Global Youth Experts(1000 Plan)Peking University Health Science Center(No. BMU2017QQ008)the State Key Laboratory of Natural and Biomimetic Drugs
文摘Interleukin 5(IL-5) is a human cytokine that regulates eosinophil growth and activation, and it plays essential roles in diseases associated with increased level of eosinophils such as asthma. Many studies have been conducted on this important glycoprotein, but all of them utilized recombinantly expressed samples. Here we describe our attempted chemical synthesis of IL-5, using protocols of Fmoc-SPPS and peptidyl hydrazide-based native chemical ligation, where the disulfide-reduced form of IL-5 is assembled from three peptide segments. Reconstitution of the protein under different folding conditions has also been investigated.
