Besides exhibiting excellent capabilities such as energy absorption,phase-transforming metamaterials offer a vast design space for achieving nonlinear constitutive relations.This is facilitated by switching between di...Besides exhibiting excellent capabilities such as energy absorption,phase-transforming metamaterials offer a vast design space for achieving nonlinear constitutive relations.This is facilitated by switching between different patterns under deformation.However,the related inverse design problem is quite challenging,due to the lack of appropriate mathematical formulation and the convergence issue in the post-buckling analysis of intermediate designs.In this work,periodic unit cells are explicitly described by the moving morphable voids method and effectively analyzed by eliminating the degrees of freedom in void regions.Furthermore,by exploring the Pareto frontiers between error and cost,an inverse design formulation is proposed for unit cells.This formulation aims to achieve a prescribed constitutive curve and is validated through numerical examples and experimental results.The design approach presented here can be extended to the inverse design of other types of mechanical metamaterials with prescribed nonlinear effective properties.展开更多
Brain tissue is one of the softest parts of the human body,composed of white matter and grey matter.The mechanical behavior of the brain tissue plays an essential role in regulating brain morphology and brain function...Brain tissue is one of the softest parts of the human body,composed of white matter and grey matter.The mechanical behavior of the brain tissue plays an essential role in regulating brain morphology and brain function.Besides,traumatic brain injury(TBI)and various brain diseases are also greatly influenced by the brain's mechanical properties.Whether white matter or grey matter,brain tissue contains multiscale structures composed of neurons,glial cells,fibers,blood vessels,etc.,each with different mechanical properties.As such,brain tissue exhibits complex mechanical behavior,usually with strong nonlinearity,heterogeneity,and directional dependence.Building a constitutive law for multiscale brain tissue using traditional function-based approaches can be very challenging.Instead,this paper proposes a data-driven approach to establish the desired mechanical model of brain tissue.We focus on blood vessels with internal pressure embedded in a white or grey matter matrix material to demonstrate our approach.The matrix is described by an isotropic or anisotropic nonlinear elastic model.A representative unit cell(RUC)with blood vessels is built,which is used to generate the stress-strain data under different internal blood pressure and various proportional displacement loading paths.The generated stress-strain data is then used to train a mechanical law using artificial neural networks to predict the macroscopic mechanical response of brain tissue under different internal pressures.Finally,the trained material model is implemented into finite element software to predict the mechanical behavior of a whole brain under intracranial pressure and distributed body forces.Compared with a direct numerical simulation that employs a reference material model,our proposed approach greatly reduces the computational cost and improves modeling efficiency.The predictions made by our trained model demonstrate sufficient accuracy.Specifically,we find that the level of internal blood pressure can greatly influence stress distribution and determine the possible related damage behaviors.展开更多
Photocatalytic conversion of solar energy into hydrogen and high value-added fine chemicals has attracted increasing attention. Herein, we demonstrate an efficient photocatalytic system for simultaneous hydrogen evolu...Photocatalytic conversion of solar energy into hydrogen and high value-added fine chemicals has attracted increasing attention. Herein, we demonstrate an efficient photocatalytic system for simultaneous hydrogen evolution and benzaldehyde production by dehydrogenation of benzyl alcohol over Nidecorated Zn_(0.5)Cd_(0.5)S solid solution under visible light. The photocatalytic system shows an excellent hydrogen production rate of 666.3 μmol h^(-1) with high stability. The optimal apparent quantum yield of52.5% is obtained at 420 nm. This noble-metal-free photocatalytic system displays much higher activity than pure Zn_(0.5)Cd_(0.5)S and Pt-loaded Zn_(0.5)Cd_(0.5)S solid solution. Further studies reveal that the metallic Ni nanocrystals play an important role in accelerating the separation of photogenerated charge carriers and the subsequent cleavage of α-C–H bond during dehydrogenation of benzyl alcohol.展开更多
The conversion of CO_(2) to methanol with high activity and high selectivity remains challenging owing to the kinetic and thermodynamic limitations associated with the low chemical reactivity exhibited by CO_(2).Herei...The conversion of CO_(2) to methanol with high activity and high selectivity remains challenging owing to the kinetic and thermodynamic limitations associated with the low chemical reactivity exhibited by CO_(2).Herein,we report a novel Cd/TiO_(2) catalyst exhibiting a methanol selectivity of 81%,a CO_(2) conversion of 15.8%,and a CH_(4) selectivity below 0.7%.A combination of experimental and computational studies revealed that the unique electronic properties exhibited by the Cd clusters supported by the TiO_(2) matrix were responsible for the high selectivity of CO_(2) hydrogenation to methanol via the HCOO*pathway at the interfacial catalytic sites.展开更多
The recently developed data-driven approach can establish the material law for nonlinear elastic composite materials(especially newly developed materials)by the generated stress-strain data under different loading pat...The recently developed data-driven approach can establish the material law for nonlinear elastic composite materials(especially newly developed materials)by the generated stress-strain data under different loading paths(Computational Mechanics,2019).Generally,the displacement(or strain)fields can be obtained relatively easier using digital image correlation(DIC)technique experimentally,but the stress field is hard to be measured.This situation limits the applicability of the proposed data-driven approach.In this paper,a method based on artificial neural network(ANN)to identify stress fields and further obtain the material law of nonlinear elastic materials is presented,which can make the proposed data-driven approach more practical.A numerical example is given to prove the validity of the method.The limitations of the proposed approach are also discussed.展开更多
In this paper,a data-driven method to model the three-dimensional engineering structure under the cyclic load with the one-dimensional stress-strain data is proposed.In this method,one-dimensional stress-strain data o...In this paper,a data-driven method to model the three-dimensional engineering structure under the cyclic load with the one-dimensional stress-strain data is proposed.In this method,one-dimensional stress-strain data obtained under uniaxial load and different loading history is learned offline by gate recurrent unit(GRU)network.The learned constitutive model is embedded into the general finite element framework through data expansion from one dimension to three dimensions,which can perform stress updates under the three-dimensional setting.The proposed method is then adopted to drive numerical solutions of boundary value problems for engineering structures.Compared with direct numerical simulations using the J2 plasticity model,the stress-strain response of beam structure with elastoplastic materials under forward loading,reverse loading and cyclic loading were predicted accurately.Loading path dependent response of structure was captured and the effectiveness of the proposed method is verified.The shortcomings of the proposed method are also discussed.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
Aiming at accessing polyethylene-bearing in-chain degradable functionality,copolymerization of carbon dioxide(CO_(2))with ethylene has long been recognized as a significant but highly challenging transformation.Nevert...Aiming at accessing polyethylene-bearing in-chain degradable functionality,copolymerization of carbon dioxide(CO_(2))with ethylene has long been recognized as a significant but highly challenging transformation.Nevertheless,most trials have resulted in ethylene homopolymerization because of the endothermic property and high energy barriers of CO_(2)insertion during polymer chain propagation.Here we report an unprecedented tandem reaction protocol for the synthesis of polyethylenes with in-chain carbonyls from CO_(2)and ethylene by the combination of photocatalytic CO_(2)reduction and palladium-catalyzed coordination/insertion polymerization.This protocol provides an easy way to adjust the carbonyl content(from 0.13 to 12 mol%)and insertion selectivity(up to 99%isolated carbonyls)of the polyethylene copolymers,which enables the polymers tomaintain the main properties of highdensity polyethylene and simultaneously endows them with good photodegradability.In addition,besides apolar polyethylene copolymers,polar-functionalized polyethylenes with in-chain isolated carbonyls can also be synthesized from CO_(2),ethylene and a polar monomer using the same protocol.We believe our present work sheds new light on the synthesis of degradable polyethylenes by employing CO_(2)as a green carbonyl source.展开更多
Background and Aims:Decompensated cirrhotic patients with hepatitis C(HCV)are often under-represented in clinical trials.We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir(SOF)-based regimens in...Background and Aims:Decompensated cirrhotic patients with hepatitis C(HCV)are often under-represented in clinical trials.We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir(SOF)-based regimens in these patients.Methods:We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020.Outcomes of interest were sustained virologic response(SVR)and safety of SOFbased regimens in decompensated HCV patients.Two reviewers independently performed the study selection and data extraction.Results:We included 33 studies that enrolled 5,302 HCV patients.The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1%(95%CI:82.8–87.3).Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR(91.0%,95%CI:87.7–93.9)than that of SOF/ledipasvir±ribavirin[(86.3%,95%CI:84.6–87.8);p=0.004],or on SOF/daclatasvir±ribavirin(82.4%,95%CI:78.2–86.2%;p<0.001).Adding ribavirin to SOFbased regimens(pooled SVR 84.9%,95%CI:81.7–87.9)did not significantly increase the SVR[83.8%(95%CI:76.8–89.8%;p=0.76)]in decompensated patients,which was also true in subgroup analyses for each regimen within the same treatment duration.However,adding ribavirin significantly increased the frequency of adverse events from 52.9%(95%CI:28.0–77.1)to 89.2%(95%CI:68.1–99.9)and frequency of severe events.The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1%(95%CI:1.5–5.0)and 4.6%(95%CI:3.1–6.3),respectively.The overall heterogeneity was high.There was no publication bias.Conclusions:The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy,with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.展开更多
Seed oil content(SOC)is a highly important and complex trait in oil crops.Here,we decipher the genetic basis of natural variation in SOC of Brassica napus by genome-and transcriptome-wide association studies using 505...Seed oil content(SOC)is a highly important and complex trait in oil crops.Here,we decipher the genetic basis of natural variation in SOC of Brassica napus by genome-and transcriptome-wide association studies using 505 inbred lines.We mapped reliable quantitative trait loci(QTLs)that control SOC in eight environments,evaluated the effect of each QTL on SOC,and analyzed selection in QTL regions during breeding.Six-hundred and ninety-two genes and four gene modules significantly associated with SOC were identified by analyzing population transcriptomes from seeds.A gene prioritization framework,POCKET(prioritizing the candidate genes by incorporating information on knowledge-based gene sets,effects of variants,genome-wide association studies,and transcriptome-wide association studies),was implemented to determine the causal genes in the QTL regions based on multi-omic datasets.A pair of homologous genes,BnPMT6s,in two QTLs were identified and experimentally demonstrated to negatively regulate SOC.This study provides rich genetic resources for improving SOC and valuable insights toward understanding the complex machinery that directs oil accumulation in the seeds of B.napus and other oil crops.展开更多
Radical/radical cross-coupling represents a straightforward way for the construction of new chemical bonds in theory and has received more and more attention over the past several years. Until now, it is challenging t...Radical/radical cross-coupling represents a straightforward way for the construction of new chemical bonds in theory and has received more and more attention over the past several years. Until now, it is challenging to achieve the selective bond formation between two transient radicals since selective radical cross-coupling usually happens between persistent radical and transient radical. However, the number of persistent radicals is much less than that of transient radicals. These issues limit the application of radical/radical cross-coupling in the construction of new chemical bonds. To solve this, we proposed a novel strategy ‘‘tuning radical reactivity" that could tune transient radical into persistent radical. This paper will introduce the concept and recent developments of ‘‘tuning radical reactivity".展开更多
Summary of main observation and conclusion Selective oxidative C-H sulfenylation of imidazopyridine heterocycles is achieved using an undivided electrolytic cell.The reaction avoids the use of stoichiometric amount of...Summary of main observation and conclusion Selective oxidative C-H sulfenylation of imidazopyridine heterocycles is achieved using an undivided electrolytic cell.The reaction avoids the use of stoichiometric amount of external chemical oxidant and produces hydrogen gas as the only byproduct. Both aryl and aliphatic thiols demonstrate good reactivity for C-S bond formation.展开更多
Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the fir...Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the first example of an isopeptide mimic for the branched Ub chains,which have recently emerged as an interesting category of Ub modifications. Our strategy comprised the El-dependent synthesis of the Ub conjugate of aminoethanethiol, followed by disulfide formation with Ub(K11 C, K48 C). The structure of the synthetic isopeptide bond mimics was verified by the crystal structure of Ub_3^(11/48)(S-S). Deubiquitination and pulldown assays indicated that the synthetic Ub_3^(11/48)(S-S) could be hydrolyzed by linkage-specific deubiquitinases(K11-specific Cezanne and K48-specific OTUB1), and recognized by proteasomal ubiquitin receptor S5 a.展开更多
Coupling reaction usually refers to the direct C–C bond formation between two carbon fragments.Generally, cross-coupling reactions between nucleophiles and electrophiles have been extensively studied and become the c...Coupling reaction usually refers to the direct C–C bond formation between two carbon fragments.Generally, cross-coupling reactions between nucleophiles and electrophiles have been extensively studied and become the classic model for bond constructions. Another reaction model, bond formation from two nucleophiles through oxidative cross-coupling, has received more and more attention over the past few years. This paper will discuss the concept of oxidative cross-coupling and give an overview of its recent development.展开更多
As one of the most widely existing post-translational modification models, ubiquitination regulates diverse cellular activities. In eukaryotes, K-branched ubiquitin chains play key roles in cell cycle and protein qual...As one of the most widely existing post-translational modification models, ubiquitination regulates diverse cellular activities. In eukaryotes, K-branched ubiquitin chains play key roles in cell cycle and protein quality control. However, the structural and biochemical properties of K-branched ubiquitin chains have not been well examined. Here we employed the synthetic linkage-and length-defined K-branched ubiquitin chains to examine their binding and hydrolysis properties in vitro. Quantitatively affinity determination of ubiquitin chains to the proteasome ubiquitin receptor S5 a indicated that the S5 a exhibited preference binding to K-branched chains over K-linked chains, but not K-conjugated chains. In addition, deubiquitination experiments were carried out and the results showed that K-branched chains were preferably hydrolyzed by proteasome-associated deubiquitinase Rpnll than homotypic Kor K-linked chains.展开更多
Orthotropic nonlinear elastic materials are common in nature and widely used by various industries.However,there are only limited constitutive models available in today's commercial software(e.g.,ABAQUS,ANSYS,etc....Orthotropic nonlinear elastic materials are common in nature and widely used by various industries.However,there are only limited constitutive models available in today's commercial software(e.g.,ABAQUS,ANSYS,etc.)that adequately describe their mechanical behavior.Moreover,the material parameters in these constitutive models are also difficult to calibrate through low-cost,widely available experimental setups.Therefore,it is paramount to develop new ways to model orthotropic nonlinear elastic materials.In this work,a data-driven orthotropic nonlinear elastic(DDONE)approach is proposed,which builds the constitutive response from stress–strain data sets obtained from three designed uniaxial tensile experiments.The DDONE approach is then embedded into a finite element(FE)analysis framework to solve boundary-value problems(BVPs).Illustrative examples(e.g.,structures with an orthotropic nonlinear elastic material)are presented,which agree well with the simulation results based on the reference material model.The DDONE approach generally makes accurate predictions,but it may lose accuracy when certain stress–strain states that appear in the engineering structure depart significantly from those covered in the data sets.Our DDONE approach is thus further strengthened by a mapping function,which is verified by additional numerical examples that demonstrate the effectiveness of our modified approach.Moreover,artificial neural networks(ANNs)are employed to further improve the computational efficiency and stability of the proposed DDONE approach.展开更多
基金supported by the National Natural Science Foun-dation of China(Grant Nos.12002073 and 12372122)the National Key Research and Development Plan of China(Grant No.2020YFB 1709401)+2 种基金the Science Technology Plan of Liaoning Province(Grant No.2023JH2/101600044)the Liaoning Revitalization Talents Pro-gram(Grant No.XLYC2001003)111 Project of China(Grant No.B14013).
文摘Besides exhibiting excellent capabilities such as energy absorption,phase-transforming metamaterials offer a vast design space for achieving nonlinear constitutive relations.This is facilitated by switching between different patterns under deformation.However,the related inverse design problem is quite challenging,due to the lack of appropriate mathematical formulation and the convergence issue in the post-buckling analysis of intermediate designs.In this work,periodic unit cells are explicitly described by the moving morphable voids method and effectively analyzed by eliminating the degrees of freedom in void regions.Furthermore,by exploring the Pareto frontiers between error and cost,an inverse design formulation is proposed for unit cells.This formulation aims to achieve a prescribed constitutive curve and is validated through numerical examples and experimental results.The design approach presented here can be extended to the inverse design of other types of mechanical metamaterials with prescribed nonlinear effective properties.
文摘Brain tissue is one of the softest parts of the human body,composed of white matter and grey matter.The mechanical behavior of the brain tissue plays an essential role in regulating brain morphology and brain function.Besides,traumatic brain injury(TBI)and various brain diseases are also greatly influenced by the brain's mechanical properties.Whether white matter or grey matter,brain tissue contains multiscale structures composed of neurons,glial cells,fibers,blood vessels,etc.,each with different mechanical properties.As such,brain tissue exhibits complex mechanical behavior,usually with strong nonlinearity,heterogeneity,and directional dependence.Building a constitutive law for multiscale brain tissue using traditional function-based approaches can be very challenging.Instead,this paper proposes a data-driven approach to establish the desired mechanical model of brain tissue.We focus on blood vessels with internal pressure embedded in a white or grey matter matrix material to demonstrate our approach.The matrix is described by an isotropic or anisotropic nonlinear elastic model.A representative unit cell(RUC)with blood vessels is built,which is used to generate the stress-strain data under different internal blood pressure and various proportional displacement loading paths.The generated stress-strain data is then used to train a mechanical law using artificial neural networks to predict the macroscopic mechanical response of brain tissue under different internal pressures.Finally,the trained material model is implemented into finite element software to predict the mechanical behavior of a whole brain under intracranial pressure and distributed body forces.Compared with a direct numerical simulation that employs a reference material model,our proposed approach greatly reduces the computational cost and improves modeling efficiency.The predictions made by our trained model demonstrate sufficient accuracy.Specifically,we find that the level of internal blood pressure can greatly influence stress distribution and determine the possible related damage behaviors.
基金financially supported by the National Key Research and Development Program of China(2017YFA0402800)the National Natural Science Foundation of China(grant nos.51772285,21473170)the Fundamental Research Funds for the Central Universities
文摘Photocatalytic conversion of solar energy into hydrogen and high value-added fine chemicals has attracted increasing attention. Herein, we demonstrate an efficient photocatalytic system for simultaneous hydrogen evolution and benzaldehyde production by dehydrogenation of benzyl alcohol over Nidecorated Zn_(0.5)Cd_(0.5)S solid solution under visible light. The photocatalytic system shows an excellent hydrogen production rate of 666.3 μmol h^(-1) with high stability. The optimal apparent quantum yield of52.5% is obtained at 420 nm. This noble-metal-free photocatalytic system displays much higher activity than pure Zn_(0.5)Cd_(0.5)S and Pt-loaded Zn_(0.5)Cd_(0.5)S solid solution. Further studies reveal that the metallic Ni nanocrystals play an important role in accelerating the separation of photogenerated charge carriers and the subsequent cleavage of α-C–H bond during dehydrogenation of benzyl alcohol.
文摘The conversion of CO_(2) to methanol with high activity and high selectivity remains challenging owing to the kinetic and thermodynamic limitations associated with the low chemical reactivity exhibited by CO_(2).Herein,we report a novel Cd/TiO_(2) catalyst exhibiting a methanol selectivity of 81%,a CO_(2) conversion of 15.8%,and a CH_(4) selectivity below 0.7%.A combination of experimental and computational studies revealed that the unique electronic properties exhibited by the Cd clusters supported by the TiO_(2) matrix were responsible for the high selectivity of CO_(2) hydrogenation to methanol via the HCOO*pathway at the interfacial catalytic sites.
基金the support from the National Natural Science Foundation of China (Grant 11872139)the support from the National Natural Science Foundation of China (Grants 11732004 and 11821202)Program for Changjiang Scholars, Innovative Research Team in University (PCSIRT)
文摘The recently developed data-driven approach can establish the material law for nonlinear elastic composite materials(especially newly developed materials)by the generated stress-strain data under different loading paths(Computational Mechanics,2019).Generally,the displacement(or strain)fields can be obtained relatively easier using digital image correlation(DIC)technique experimentally,but the stress field is hard to be measured.This situation limits the applicability of the proposed data-driven approach.In this paper,a method based on artificial neural network(ANN)to identify stress fields and further obtain the material law of nonlinear elastic materials is presented,which can make the proposed data-driven approach more practical.A numerical example is given to prove the validity of the method.The limitations of the proposed approach are also discussed.
文摘In this paper,a data-driven method to model the three-dimensional engineering structure under the cyclic load with the one-dimensional stress-strain data is proposed.In this method,one-dimensional stress-strain data obtained under uniaxial load and different loading history is learned offline by gate recurrent unit(GRU)network.The learned constitutive model is embedded into the general finite element framework through data expansion from one dimension to three dimensions,which can perform stress updates under the three-dimensional setting.The proposed method is then adopted to drive numerical solutions of boundary value problems for engineering structures.Compared with direct numerical simulations using the J2 plasticity model,the stress-strain response of beam structure with elastoplastic materials under forward loading,reverse loading and cyclic loading were predicted accurately.Loading path dependent response of structure was captured and the effectiveness of the proposed method is verified.The shortcomings of the proposed method are also discussed.
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 Natural Science Foundation of China(grant nos.21890730,21890733,and 22231007)the Program for Basic Research of Shanghai Science and Technology Commission(grant no.19JC1410400)+2 种基金the Fundamental Research Funds for the Central Universities(grant no.23X010301599)the Shanghai Pujiang Program(grant no.21PJ1406500)the China Postdoctoral Science Foundation(grant no.2022M722073).
文摘Aiming at accessing polyethylene-bearing in-chain degradable functionality,copolymerization of carbon dioxide(CO_(2))with ethylene has long been recognized as a significant but highly challenging transformation.Nevertheless,most trials have resulted in ethylene homopolymerization because of the endothermic property and high energy barriers of CO_(2)insertion during polymer chain propagation.Here we report an unprecedented tandem reaction protocol for the synthesis of polyethylenes with in-chain carbonyls from CO_(2)and ethylene by the combination of photocatalytic CO_(2)reduction and palladium-catalyzed coordination/insertion polymerization.This protocol provides an easy way to adjust the carbonyl content(from 0.13 to 12 mol%)and insertion selectivity(up to 99%isolated carbonyls)of the polyethylene copolymers,which enables the polymers tomaintain the main properties of highdensity polyethylene and simultaneously endows them with good photodegradability.In addition,besides apolar polyethylene copolymers,polar-functionalized polyethylenes with in-chain isolated carbonyls can also be synthesized from CO_(2),ethylene and a polar monomer using the same protocol.We believe our present work sheds new light on the synthesis of degradable polyethylenes by employing CO_(2)as a green carbonyl source.
基金supported by a research grant from the Capital health development research project (grant number:2020-1-3011)a grant from the Beijing Youan Hospital,Capital Medical University in 2018 (grant number:YNKTTS20180105)a grant from the Beijing Municipal Administration of Hospitals Incubating Program in 2018 (grant number:PX2018058).
文摘Background and Aims:Decompensated cirrhotic patients with hepatitis C(HCV)are often under-represented in clinical trials.We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir(SOF)-based regimens in these patients.Methods:We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020.Outcomes of interest were sustained virologic response(SVR)and safety of SOFbased regimens in decompensated HCV patients.Two reviewers independently performed the study selection and data extraction.Results:We included 33 studies that enrolled 5,302 HCV patients.The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1%(95%CI:82.8–87.3).Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR(91.0%,95%CI:87.7–93.9)than that of SOF/ledipasvir±ribavirin[(86.3%,95%CI:84.6–87.8);p=0.004],or on SOF/daclatasvir±ribavirin(82.4%,95%CI:78.2–86.2%;p<0.001).Adding ribavirin to SOFbased regimens(pooled SVR 84.9%,95%CI:81.7–87.9)did not significantly increase the SVR[83.8%(95%CI:76.8–89.8%;p=0.76)]in decompensated patients,which was also true in subgroup analyses for each regimen within the same treatment duration.However,adding ribavirin significantly increased the frequency of adverse events from 52.9%(95%CI:28.0–77.1)to 89.2%(95%CI:68.1–99.9)and frequency of severe events.The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1%(95%CI:1.5–5.0)and 4.6%(95%CI:3.1–6.3),respectively.The overall heterogeneity was high.There was no publication bias.Conclusions:The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy,with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.11821202,12002073,and 12002077)the National Key Research and Development Plan(Grant No.2020YFB1709400)+3 种基金Liaoning Revitalization Talents Program(Grant Nos.XLYC2001003 and XLYC1907119)Dalian Talent Innovation Program(Grant No.2020RQ099)the Fundamental Research Funds for the Central Universities(Grant Nos.DUT20RC(3)020,DUT21RC(3)076,and DUT22QN238)111 Project(Grant No.B14013).
基金This study was supported by the National Key Research and Development Plan of China(2016YFD0101000,2017YFE0104800)the National Natural Science Foundation of China(32070559,31871658).
文摘Seed oil content(SOC)is a highly important and complex trait in oil crops.Here,we decipher the genetic basis of natural variation in SOC of Brassica napus by genome-and transcriptome-wide association studies using 505 inbred lines.We mapped reliable quantitative trait loci(QTLs)that control SOC in eight environments,evaluated the effect of each QTL on SOC,and analyzed selection in QTL regions during breeding.Six-hundred and ninety-two genes and four gene modules significantly associated with SOC were identified by analyzing population transcriptomes from seeds.A gene prioritization framework,POCKET(prioritizing the candidate genes by incorporating information on knowledge-based gene sets,effects of variants,genome-wide association studies,and transcriptome-wide association studies),was implemented to determine the causal genes in the QTL regions based on multi-omic datasets.A pair of homologous genes,BnPMT6s,in two QTLs were identified and experimentally demonstrated to negatively regulate SOC.This study provides rich genetic resources for improving SOC and valuable insights toward understanding the complex machinery that directs oil accumulation in the seeds of B.napus and other oil crops.
基金supported by the National Natural Science Foundation of China(21390402,21520102003)the Hubei Provincial Natural Science Foundation(2017CFA010)The Program of Introducing Talents of Discipline to Universities of China(111 Program)
文摘Radical/radical cross-coupling represents a straightforward way for the construction of new chemical bonds in theory and has received more and more attention over the past several years. Until now, it is challenging to achieve the selective bond formation between two transient radicals since selective radical cross-coupling usually happens between persistent radical and transient radical. However, the number of persistent radicals is much less than that of transient radicals. These issues limit the application of radical/radical cross-coupling in the construction of new chemical bonds. To solve this, we proposed a novel strategy ‘‘tuning radical reactivity" that could tune transient radical into persistent radical. This paper will introduce the concept and recent developments of ‘‘tuning radical reactivity".
基金the National Natural Science Foundation of China (21390402,21520102003)the Hubei Province Natural Science Foundation of China (2017CFA010)The Program of Introducing Talents of Discipline to Universities of China (111 Program)was also appreciated.
文摘Summary of main observation and conclusion Selective oxidative C-H sulfenylation of imidazopyridine heterocycles is achieved using an undivided electrolytic cell.The reaction avoids the use of stoichiometric amount of external chemical oxidant and produces hydrogen gas as the only byproduct. Both aryl and aliphatic thiols demonstrate good reactivity for C-S bond formation.
基金supported by the National Key R&D Program of China(2017YFA0505200)the National Natural Science Foundation of China(91753205,21532004,21761142008)the Program of Introducing Talents of Discipline to Universities of China(B16028)
文摘Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the first example of an isopeptide mimic for the branched Ub chains,which have recently emerged as an interesting category of Ub modifications. Our strategy comprised the El-dependent synthesis of the Ub conjugate of aminoethanethiol, followed by disulfide formation with Ub(K11 C, K48 C). The structure of the synthetic isopeptide bond mimics was verified by the crystal structure of Ub_3^(11/48)(S-S). Deubiquitination and pulldown assays indicated that the synthetic Ub_3^(11/48)(S-S) could be hydrolyzed by linkage-specific deubiquitinases(K11-specific Cezanne and K48-specific OTUB1), and recognized by proteasomal ubiquitin receptor S5 a.
基金supported by the National Basic Research Program of China(2012CB725302)the National Natural Science Foundation of China(21390400,21272180,21302148)+1 种基金the Research Fund for the Doctoral Program of Higher Education of China(20120141130002)the Ministry of Science and Technology of China(2012YQ120060)
文摘Coupling reaction usually refers to the direct C–C bond formation between two carbon fragments.Generally, cross-coupling reactions between nucleophiles and electrophiles have been extensively studied and become the classic model for bond constructions. Another reaction model, bond formation from two nucleophiles through oxidative cross-coupling, has received more and more attention over the past few years. This paper will discuss the concept of oxidative cross-coupling and give an overview of its recent development.
基金supported by the National Natural Science Foundation of China(Nos. U1732161, 91753120)
文摘As one of the most widely existing post-translational modification models, ubiquitination regulates diverse cellular activities. In eukaryotes, K-branched ubiquitin chains play key roles in cell cycle and protein quality control. However, the structural and biochemical properties of K-branched ubiquitin chains have not been well examined. Here we employed the synthetic linkage-and length-defined K-branched ubiquitin chains to examine their binding and hydrolysis properties in vitro. Quantitatively affinity determination of ubiquitin chains to the proteasome ubiquitin receptor S5 a indicated that the S5 a exhibited preference binding to K-branched chains over K-linked chains, but not K-conjugated chains. In addition, deubiquitination experiments were carried out and the results showed that K-branched chains were preferably hydrolyzed by proteasome-associated deubiquitinase Rpnll than homotypic Kor K-linked chains.
基金The support of Project MKF20210033 is acknowledged.
文摘Orthotropic nonlinear elastic materials are common in nature and widely used by various industries.However,there are only limited constitutive models available in today's commercial software(e.g.,ABAQUS,ANSYS,etc.)that adequately describe their mechanical behavior.Moreover,the material parameters in these constitutive models are also difficult to calibrate through low-cost,widely available experimental setups.Therefore,it is paramount to develop new ways to model orthotropic nonlinear elastic materials.In this work,a data-driven orthotropic nonlinear elastic(DDONE)approach is proposed,which builds the constitutive response from stress–strain data sets obtained from three designed uniaxial tensile experiments.The DDONE approach is then embedded into a finite element(FE)analysis framework to solve boundary-value problems(BVPs).Illustrative examples(e.g.,structures with an orthotropic nonlinear elastic material)are presented,which agree well with the simulation results based on the reference material model.The DDONE approach generally makes accurate predictions,but it may lose accuracy when certain stress–strain states that appear in the engineering structure depart significantly from those covered in the data sets.Our DDONE approach is thus further strengthened by a mapping function,which is verified by additional numerical examples that demonstrate the effectiveness of our modified approach.Moreover,artificial neural networks(ANNs)are employed to further improve the computational efficiency and stability of the proposed DDONE approach.
