Although the single-particle model enhanced with electrolyte dynamics(SPMe)is simplified from the pseudo-twodimensional(P2D)electrochemical model for lithium-ion batteries,it is difficult to solve the partial differen...Although the single-particle model enhanced with electrolyte dynamics(SPMe)is simplified from the pseudo-twodimensional(P2D)electrochemical model for lithium-ion batteries,it is difficult to solve the partial differential equations of solid–liquid phases in real-time applications.Moreover,working temperatures have a heavy impact on the battery behavior.Hence,a thermal-coupling SPMe is constructed.Herein,a lumped thermal model is established to estimate battery temperatures.The order of the SPMe model is reduced by using both transfer functions and truncation techniques and merged with Arrhenius equations for thermal effects.The polarization voltage drop is then modified through the use of test data because its original model is unreliable theoretically.Finally,the coupling-model parameters are extracted using genetic algorithms.Experimental results demonstrate that the proposed model produces average errors of about 42 mV under 15 constant current conditions and 15 mV under nine dynamic conditions,respectively.This new electrochemicalthermal coupling model is reliable and expected to be used for onboard applications.展开更多
Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional land...Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional landrace‘Chinese Herbal Medicine’.Variations between the 2.62 Gb CHM genome and that of the previously sequenced high noscapine 1(HN1)variety were also explored.Among 79,668 protein-coding genes,we functionally annotated 88.9%,compared to 68.8%reported in the HN1 genome.Gene family and 4DTv comparative analyses with three other Papaveraceae species revealed that opium poppy underwent two whole-genome duplication(WGD)events.The first of these,in ancestral Ranunculales,expanded gene families related to characteristic secondary metabolite production and disease resistance.The more recent species-specific WGD mediated by transposable elements resulted in massive genome expansion.Genes carrying structural variations and large-effect variants associated with agronomically different phenotypes between CHM and HN1 that were identified through our transcriptomic comparison of multiple organs and developmental stages can enable the development of new varieties.These genomic and transcriptomic analyses will provide a valuable resource that informs future basic and agricultural studies of the opium poppy.展开更多
This paper studies a deconvolved Chebyshev beamforming(Dcv-Che-BF)method.Compared with other deconvolution beamforming methods,Dcv-Che-BF can preset sidelobe levels according to the actual situation,which can achieve ...This paper studies a deconvolved Chebyshev beamforming(Dcv-Che-BF)method.Compared with other deconvolution beamforming methods,Dcv-Che-BF can preset sidelobe levels according to the actual situation,which can achieve higher resolution performance.However,the performance of Dcv-Che-BF was not necessarily better with a lower preset sidelobe level in the presence of noise.Instead,it was much better when the preset side lobe level matched the signal to noise ratio of the signal.The performance of the Dcv-Che-BF method with different preset sidelobe levels was analyzed using simulation.The Dcv-Che-BF method achieved a lower sidelobe level and better resolution capability when the preset sidelobe level was slightly greater than the noise background level.To validate the feasibility and performance of the proposed method,computer simulations and sea trials were analyzed.The results show that the Dcv-Che-BF method is a robust high-resolution beamforming method that can achieve a narrow mainlobe and low sidelobe.展开更多
As auxins are among the most important phytohormones,the regulation of auxin homeostasis is complex.Generally,auxin conjugates,especially IAA glucosides,are predominant at high auxin levels.Previous research on termin...As auxins are among the most important phytohormones,the regulation of auxin homeostasis is complex.Generally,auxin conjugates,especially IAA glucosides,are predominant at high auxin levels.Previous research on terminal glucosylation focused mainly on the O-position,while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001.In our study,IAA-Asp-N-glucoside was found to be specifically abundant(as high as 4.13 mg/g)in the seeds of 58 ginkgo cultivars.Furthermore,a novel N-glucosyltransferase,termed GbNGT1,was identified via differential transcriptome analysis and in vitro enzymatic testing.It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides.The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates.Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo.The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana.The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.展开更多
Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those with a family history of Alcohol Dependence (AD) may be related to structural diffe...Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods: Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results: High-risk subjects showed poorer Working Memory functioning. Caudate volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions: Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.展开更多
Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high in...Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.展开更多
The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing.However,natural nucleases of this system often exhibit low efficiency,limiting their application.Here,we used structure-guided...The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing.However,natural nucleases of this system often exhibit low efficiency,limiting their application.Here,we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease,Cas12i3.As a result,we developed Cas-SF01,a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells.Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases.Compared to natural Cas12i3,Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs.In addition,we identified an amino acid substitution,D876R,that markedly reduced the off-target effect while maintaining high on-target activity,leading to the development of CasSF01^(HiFi)(high-fidelity Cas-SF01).Finally,we show that Cas-SF01 has high gene editing activities in mice and plants.Our results suggest that CasSF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.展开更多
Recently,advanced sensing techniques ensure a large number of multivariate sensing data for intelligent fault diagnosis of machines.Given the advantage of obtaining accurate diagnosis results,multi-sensor fusion has l...Recently,advanced sensing techniques ensure a large number of multivariate sensing data for intelligent fault diagnosis of machines.Given the advantage of obtaining accurate diagnosis results,multi-sensor fusion has long been studied in the fault diagnosis field.However,existing studies suffer from two weaknesses.First,the relations of multiple sensors are either neglected or calculated only to improve the diagnostic accuracy of fault types.Second,the localization for multi-source faults is seldom investigated,although locating the anomaly variable over multivariate sensing data for certain types of faults is desirable.This article attempts to overcome the above weaknesses by proposing a global method to recognize fault types and localize fault sources with the help of multi-sensor relations(MSRs).First,an MSR model is developed to learn MSRs automatically and further obtain fault recognition results.Second,centrality measures are employed to analyze the MSR graphs learned by the MSR model,and fault sources are therefore determined.The proposed method is demonstrated by experiments on an induction motor and a centrifugal pump.Results show the proposed method’s validity in diagnosing fault types and sources.展开更多
While crop yields have historically increased,drought resistance has become a major concern in the context of global climate change.The trade-off between crop yield and drought resistance is a common phenomenon;howeve...While crop yields have historically increased,drought resistance has become a major concern in the context of global climate change.The trade-off between crop yield and drought resistance is a common phenomenon;however,the underlying molecular modulators remain undetermined.Through genome-wide association study,we revealed that three non-synonymous variants in a drought-resistant allele of ZmSRO1d-R resulted in plasma membrane localization and enhanced mono-ADP-ribosyltransferase activity of ZmSRO1d toward ZmRBOHC,which increased reactive oxygen species(ROS)levels in guard cells and promoted stomatal closure.ZmSRO1d-R enhanced plant drought resilience and protected grain yields under drought conditions,but it led to yield drag under favorable conditions.In contrast,loss-of-function mutants of ZmRBOHC showed remarkably increased yields under well-watered conditions,whereas they showed compromised drought resistance.Interestingly,by analyzing 189 teosinte accessions,we found that the ZmSRO1d-R allele was present in teosinte but was selected against during maize domestication and modern breeding.Collectively,our work suggests that the allele frequency reduction of ZmSRO1d-R in breeding programs may have compromised maize drought resistance while increased yields.Therefore,introduction of the ZmSRO1d-R allele into modern maize cultivars would contribute to food security under drought stress caused by global climate change.展开更多
Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) ...Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) located in the env gene through their cis-acting targets. We have identified and characterized a 72 bp TBS (Borf-1) responsive element located in BFV3026, internal promoter (TREIP) by deletion mutant and transient expression assay. This cis-acting target element in the internal promoter has the properties of a transcriptional enhancer which functions independently of its orientation, position and also in heterologous promoters (BFV LTR and bovine immunodeficiency virus, BIV LTR). Alignments reveal that there are positional similarity and sequence homology among BFV TREIP, SFV-1 TREIP proximal element and SFV-3 TREIPH, which suggests that this kind of cis-acting elements possesses some common functional character.展开更多
Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T...Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxF"for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.展开更多
Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown ...Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown that mimosine can also inhibit the replication of Xenopus ribo-some DNA (rDNA) plasmid reversibly. The high structure similarity between mimosine展开更多
In this study,Mn catalysts have been designed based on manganese oxide octahedral molecular sieve(OMS-2) supports to optimize the catalytic activity in the degradation of organic pollutants.Herein,two different synthe...In this study,Mn catalysts have been designed based on manganese oxide octahedral molecular sieve(OMS-2) supports to optimize the catalytic activity in the degradation of organic pollutants.Herein,two different synthetic strategies:Pre-incorporation vs.wet-impregnation have been employed to synthesize[PW]-OMS-2 and [PW]/OMS-2.For [PW]-OMS-2,energy dispersive X-ray spectroscopy(EDX) confirmed that dispersed granular phosphotungstic acid attached and located at the surface of OMS-2,meanwhile some W atoms have been doped into frameworks of OMS-2.However,for [PW]/OMS-2,the W atoms cannot enter the OMS-2 frameworks.A correlation has been established between the different synthetic strategies and catalytic activities.The [PW]-OMS-2 is the most highly effective and stable over than[PW]/OMS-2 and OMS-2 itself for the organic pollutants removal.This may be caused not only by the synergetic effect of [PW] and OMS-2,but also by doping W into frameworks of OMS-2.Therefore,this work provides a new environmentally-friendly and heterogeneous PMS activator and it may be put into practice to degrade organic pollutants.展开更多
Most of our learning comes from other people or from our own experience. For instance, when a taxi driver is seeking passengers on an unknown road in a large city, what should the driver do? Alternatives include crui...Most of our learning comes from other people or from our own experience. For instance, when a taxi driver is seeking passengers on an unknown road in a large city, what should the driver do? Alternatives include cruising around the road or waiting for a time period at the roadside in the hopes of finding a passenger or just leaving for another road enroute to a destination he knows (e.g., hotel taxi rank)? This is an interesting problem that arises everyday in cities all over the world. There could be different answers to the question poised above, but one fundamental problem is how the driver learns about the likelihood of finding passengers on a road that is new to him (as he has not picked up or dropped off passengers there before). Our observation from large scale taxi driver trace data is that a driver not only learns from his own experience but through interactions with other drivers. In this paper, we first formally define this problem as socialized information learning (SIL), second we propose a framework including a series of models to study how a taxi driver gathers and learns information in an uncertain environment through the use of his social network. Finally, the large scale real life data and empirical experiments confirm that our models are much more effective, efficient and scalable that prior work on this problem.展开更多
After nearly 40 years of research and control efforts,much progress has been made to accomplish the most significant achievements in antiviral drug development and cocktail therapy that has transformed the human immun...After nearly 40 years of research and control efforts,much progress has been made to accomplish the most significant achievements in antiviral drug development and cocktail therapy that has transformed the human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS)treatment regiment from having the highest mortality into a manageable chronic disease like hypertension or diabetes.展开更多
基金the financial support from the National Key Research and Development Program of China(Grant No.2021YFF0601101)。
文摘Although the single-particle model enhanced with electrolyte dynamics(SPMe)is simplified from the pseudo-twodimensional(P2D)electrochemical model for lithium-ion batteries,it is difficult to solve the partial differential equations of solid–liquid phases in real-time applications.Moreover,working temperatures have a heavy impact on the battery behavior.Hence,a thermal-coupling SPMe is constructed.Herein,a lumped thermal model is established to estimate battery temperatures.The order of the SPMe model is reduced by using both transfer functions and truncation techniques and merged with Arrhenius equations for thermal effects.The polarization voltage drop is then modified through the use of test data because its original model is unreliable theoretically.Finally,the coupling-model parameters are extracted using genetic algorithms.Experimental results demonstrate that the proposed model produces average errors of about 42 mV under 15 constant current conditions and 15 mV under nine dynamic conditions,respectively.This new electrochemicalthermal coupling model is reliable and expected to be used for onboard applications.
基金the National Science Foundation of China(Grant 81671876)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grant 2016JB024)。
文摘Opium poppy(Papaver somniferum)is a source of morphine,codeine,and semisynthetic derivatives,including oxycodone and naltrexone.Here,we report the de novo assembly and genomic analysis of P.somniferum traditional landrace‘Chinese Herbal Medicine’.Variations between the 2.62 Gb CHM genome and that of the previously sequenced high noscapine 1(HN1)variety were also explored.Among 79,668 protein-coding genes,we functionally annotated 88.9%,compared to 68.8%reported in the HN1 genome.Gene family and 4DTv comparative analyses with three other Papaveraceae species revealed that opium poppy underwent two whole-genome duplication(WGD)events.The first of these,in ancestral Ranunculales,expanded gene families related to characteristic secondary metabolite production and disease resistance.The more recent species-specific WGD mediated by transposable elements resulted in massive genome expansion.Genes carrying structural variations and large-effect variants associated with agronomically different phenotypes between CHM and HN1 that were identified through our transcriptomic comparison of multiple organs and developmental stages can enable the development of new varieties.These genomic and transcriptomic analyses will provide a valuable resource that informs future basic and agricultural studies of the opium poppy.
基金Supported by the National Natural Science Foundation of China under Grant No.61801140.
文摘This paper studies a deconvolved Chebyshev beamforming(Dcv-Che-BF)method.Compared with other deconvolution beamforming methods,Dcv-Che-BF can preset sidelobe levels according to the actual situation,which can achieve higher resolution performance.However,the performance of Dcv-Che-BF was not necessarily better with a lower preset sidelobe level in the presence of noise.Instead,it was much better when the preset side lobe level matched the signal to noise ratio of the signal.The performance of the Dcv-Che-BF method with different preset sidelobe levels was analyzed using simulation.The Dcv-Che-BF method achieved a lower sidelobe level and better resolution capability when the preset sidelobe level was slightly greater than the noise background level.To validate the feasibility and performance of the proposed method,computer simulations and sea trials were analyzed.The results show that the Dcv-Che-BF method is a robust high-resolution beamforming method that can achieve a narrow mainlobe and low sidelobe.
基金This research was supported by Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CACMS Innovation Fund,C12021A04117)the National Key R&D Program of China(2019YFC1711100)Beijing Natural Science Foundation of China(7192138),and the Fundamental Research Funds for the Central Public Welfare Research Institute of China(ZZ13-YQ-097).
文摘As auxins are among the most important phytohormones,the regulation of auxin homeostasis is complex.Generally,auxin conjugates,especially IAA glucosides,are predominant at high auxin levels.Previous research on terminal glucosylation focused mainly on the O-position,while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001.In our study,IAA-Asp-N-glucoside was found to be specifically abundant(as high as 4.13 mg/g)in the seeds of 58 ginkgo cultivars.Furthermore,a novel N-glucosyltransferase,termed GbNGT1,was identified via differential transcriptome analysis and in vitro enzymatic testing.It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides.The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates.Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo.The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana.The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.
文摘Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods: Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results: High-risk subjects showed poorer Working Memory functioning. Caudate volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions: Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.
基金National Natural Science Foundation of China(No.22274061)the 111 Project B17019.Supported by the Fundamental Research Funds for the Central Universities(No.CCNU22QN007)Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202101).
文摘Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.
基金This work was supported by Shandong BellaGen Biotechnology,and by a grant from the National Natural Science Foundation of China(32188102 to J.-K.Z.).
文摘The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing.However,natural nucleases of this system often exhibit low efficiency,limiting their application.Here,we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease,Cas12i3.As a result,we developed Cas-SF01,a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells.Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases.Compared to natural Cas12i3,Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs.In addition,we identified an amino acid substitution,D876R,that markedly reduced the off-target effect while maintaining high on-target activity,leading to the development of CasSF01^(HiFi)(high-fidelity Cas-SF01).Finally,we show that Cas-SF01 has high gene editing activities in mice and plants.Our results suggest that CasSF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.
基金supported by the National Natural Science Foundation of China(Grant No.52025056)the Fundamental Research Funds for the Central Universities.
文摘Recently,advanced sensing techniques ensure a large number of multivariate sensing data for intelligent fault diagnosis of machines.Given the advantage of obtaining accurate diagnosis results,multi-sensor fusion has long been studied in the fault diagnosis field.However,existing studies suffer from two weaknesses.First,the relations of multiple sensors are either neglected or calculated only to improve the diagnostic accuracy of fault types.Second,the localization for multi-source faults is seldom investigated,although locating the anomaly variable over multivariate sensing data for certain types of faults is desirable.This article attempts to overcome the above weaknesses by proposing a global method to recognize fault types and localize fault sources with the help of multi-sensor relations(MSRs).First,an MSR model is developed to learn MSRs automatically and further obtain fault recognition results.Second,centrality measures are employed to analyze the MSR graphs learned by the MSR model,and fault sources are therefore determined.The proposed method is demonstrated by experiments on an induction motor and a centrifugal pump.Results show the proposed method’s validity in diagnosing fault types and sources.
基金Beijing Outstanding Young Scientist Pro-gram(BJJWZYJH01201910019026)National Key Research and Devel-opment Program of China(2021YFD1200703)the National Natural Science Foundation of China(31625022,31971952).
文摘While crop yields have historically increased,drought resistance has become a major concern in the context of global climate change.The trade-off between crop yield and drought resistance is a common phenomenon;however,the underlying molecular modulators remain undetermined.Through genome-wide association study,we revealed that three non-synonymous variants in a drought-resistant allele of ZmSRO1d-R resulted in plasma membrane localization and enhanced mono-ADP-ribosyltransferase activity of ZmSRO1d toward ZmRBOHC,which increased reactive oxygen species(ROS)levels in guard cells and promoted stomatal closure.ZmSRO1d-R enhanced plant drought resilience and protected grain yields under drought conditions,but it led to yield drag under favorable conditions.In contrast,loss-of-function mutants of ZmRBOHC showed remarkably increased yields under well-watered conditions,whereas they showed compromised drought resistance.Interestingly,by analyzing 189 teosinte accessions,we found that the ZmSRO1d-R allele was present in teosinte but was selected against during maize domestication and modern breeding.Collectively,our work suggests that the allele frequency reduction of ZmSRO1d-R in breeding programs may have compromised maize drought resistance while increased yields.Therefore,introduction of the ZmSRO1d-R allele into modern maize cultivars would contribute to food security under drought stress caused by global climate change.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39970033 ) Doctoral Fund in High School (Grant No. 98005516).
文摘Bovine foamy virus encodes a transcriptional transactivitor, Tas or Borf-1, which governs the level of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) located in the env gene through their cis-acting targets. We have identified and characterized a 72 bp TBS (Borf-1) responsive element located in BFV3026, internal promoter (TREIP) by deletion mutant and transient expression assay. This cis-acting target element in the internal promoter has the properties of a transcriptional enhancer which functions independently of its orientation, position and also in heterologous promoters (BFV LTR and bovine immunodeficiency virus, BIV LTR). Alignments reveal that there are positional similarity and sequence homology among BFV TREIP, SFV-1 TREIP proximal element and SFV-3 TREIPH, which suggests that this kind of cis-acting elements possesses some common functional character.
基金We are extremely grateful to the National Centre for Protein Science Shanghai(Protein Expression and Purification System)for their instrumental support and technical assistance.We thank the staff from beamlines BL18U and BL19U1 at Shanghai Synchrotron Radiation Facility(Shanghai,China)and beamline BL41XU at SPring-8(Hyogo,Japan)for assistance during data collection.We also thank Prof.Rongguang Zhang and Dr.Jinwei Zhu for providing laboratory resources.This work was supported by Grants from the National Key Research and Development Program of China(Grant No.2017YFC0840300)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB08020200)the National Natural Science Foundation of China(Grant Nos.81520108019,31500607).
文摘Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxF"for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.
基金supported by the National Key Research and Development Program of China(2020YFB1506400)the National Natural Science Foundation of China(51922074,22075194,and 51820105003)+3 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(20KJA430010)the Tang Scholarthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Collaborative Innovation Center of Suzhou Nano Science and Technology。
文摘Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown that mimosine can also inhibit the replication of Xenopus ribo-some DNA (rDNA) plasmid reversibly. The high structure similarity between mimosine
基金supported by the National Natural Science Foundation of China (Nos.21805166,21403256 and 21573261)the 111 Project (No.D20015)+3 种基金the Engineering Research Center of Eco-environment in Three Gorges Reservoir Region,Ministry of Education,China Three Gorges University (No.KF2019-05)the Outstanding Young and Middle-Aged Science and Technology Innovation Teams,Ministry of Education,Hubei province,China (No.T2020004)the Youth Innovation Promotion Association CAS (No.2018456)LICP Cooperation Foundation for Young Scholars (No.HZJJ20-10)。
文摘In this study,Mn catalysts have been designed based on manganese oxide octahedral molecular sieve(OMS-2) supports to optimize the catalytic activity in the degradation of organic pollutants.Herein,two different synthetic strategies:Pre-incorporation vs.wet-impregnation have been employed to synthesize[PW]-OMS-2 and [PW]/OMS-2.For [PW]-OMS-2,energy dispersive X-ray spectroscopy(EDX) confirmed that dispersed granular phosphotungstic acid attached and located at the surface of OMS-2,meanwhile some W atoms have been doped into frameworks of OMS-2.However,for [PW]/OMS-2,the W atoms cannot enter the OMS-2 frameworks.A correlation has been established between the different synthetic strategies and catalytic activities.The [PW]-OMS-2 is the most highly effective and stable over than[PW]/OMS-2 and OMS-2 itself for the organic pollutants removal.This may be caused not only by the synergetic effect of [PW] and OMS-2,but also by doping W into frameworks of OMS-2.Therefore,this work provides a new environmentally-friendly and heterogeneous PMS activator and it may be put into practice to degrade organic pollutants.
基金This research was supported by the T-SET Univer- sity Transportation Center sponsored by the US Department of Transporta- tion (DTRT12-G-UTCll), and Huawei Corporation (YBCB2009041-27), and the Singapore National Research Foundation under its International Re- search Centre @ Singapore Funding Initiative and administered by the IDM Programme Office. This research was supported in part by the National Basic Research Program of China (973 Program) (2012CB316400), in part by the National Natural Science Foundation of China (Grant No. 61303160), and in part by China Postdoctoral Science Foundation (2013M530739).
文摘Most of our learning comes from other people or from our own experience. For instance, when a taxi driver is seeking passengers on an unknown road in a large city, what should the driver do? Alternatives include cruising around the road or waiting for a time period at the roadside in the hopes of finding a passenger or just leaving for another road enroute to a destination he knows (e.g., hotel taxi rank)? This is an interesting problem that arises everyday in cities all over the world. There could be different answers to the question poised above, but one fundamental problem is how the driver learns about the likelihood of finding passengers on a road that is new to him (as he has not picked up or dropped off passengers there before). Our observation from large scale taxi driver trace data is that a driver not only learns from his own experience but through interactions with other drivers. In this paper, we first formally define this problem as socialized information learning (SIL), second we propose a framework including a series of models to study how a taxi driver gathers and learns information in an uncertain environment through the use of his social network. Finally, the large scale real life data and empirical experiments confirm that our models are much more effective, efficient and scalable that prior work on this problem.
文摘After nearly 40 years of research and control efforts,much progress has been made to accomplish the most significant achievements in antiviral drug development and cocktail therapy that has transformed the human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS)treatment regiment from having the highest mortality into a manageable chronic disease like hypertension or diabetes.