Currently,detecting SARS-CoV-2 RNAs is a standard approach for COVID-19 diagnosis.However,there is an urgent need for reliable and rapid serological diagnostic methods to screen SARS-CoV-2-infected people including th...Currently,detecting SARS-CoV-2 RNAs is a standard approach for COVID-19 diagnosis.However,there is an urgent need for reliable and rapid serological diagnostic methods to screen SARS-CoV-2-infected people including those who do not have overt symptoms.Most emerging studies described serological tests based on detection of SARS-CoV-2-specific IgM and IgG.1–4 Although detection of SARS-CoV-2-specific IgA in serum has been reported in few papers,5,6 analyses of IgA levels in a larger number of COVID-19 patients are still lacking.展开更多
AIM: Human heparanase is an endo-D-glucuronidase that degrades heparan sulfate/heparin and has been implicated in a variety of biological processes. The objective was to investigate the expression of heparanase (Hps) ...AIM: Human heparanase is an endo-D-glucuronidase that degrades heparan sulfate/heparin and has been implicated in a variety of biological processes. The objective was to investigate the expression of heparanase (Hps) and basic fibroblast growth factor (bFGF) and their relationship to neoangiogenesis and metastasis of human esophageal carcinoma.METHODS: Seventy-nine patients who had undergone esophageal resection for esophageal carcinoma without preoperative treatment were included in the present study. Immunohistochemistry was used to study the expression of Hps, bFGF and microvessel density (MVD) in 79 cases of esoph-ageal carcinoma. bFGF and Hps were quantitatively detected with immunohistochemistry in 79 cases of human esopha-geal carcinoma and 19 cases of adjacent normal human esophageal carcinoma. Cd34 was used to explore the MVD as a marker of endothelial cells. RESULTS: Hps and bFGF expression in tumor tissue, being remarkably higher than that in normal esophageal tissue, were significantly correlated with clinicopathological features (depth of invasion, lymph-node metastasis and TNM stage) and MVD.CONCLUSION: The results of this study suggest that thecoexpression of Hps and bFGF plays a key role in angiogenesis, invasion and metastasis of esophageal carcinoma. Hps and bFGF may serve as a predictor of progression in esophageal carcinoma. The expression of heparanase in esophageal carcinoma enhances growth, invasion, and angiogenesis of the tumor, and bFGF seemsto be a potent antigenic factor for esophageal carcinoma.展开更多
3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is l...3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is lower bainite plates or polygonal ferrite containing quantities of dispersed cementite particles, mixed with a few of low carbon martensite laths or ferrite, depending on the heat input. The hardness and the tensile strength of the weld metal are higher than those of the base metal, and monotonously increase as the heat input decreases. No softened zone exists in heat affected zone (HAZ). Compared with the base metal, although the grains of laser weld are much larger, the toughness of the weld metal is higher within a large range of heat input. Furthermore, as the heat input increases, the toughness of the weld metal rises to a maximum value, at which point the percentage of lower bainite is the highest, and then drops.展开更多
In order to simulate the flow control problem by using Nanosecond Pulsed Dielectric Barrier Discharge(NSDBD),a one-zone inhomogeneous phenomenological model is constructed based on the experimental and theoretical res...In order to simulate the flow control problem by using Nanosecond Pulsed Dielectric Barrier Discharge(NSDBD),a one-zone inhomogeneous phenomenological model is constructed based on the experimental and theoretical results.The model is coupled with the unsteady Navier-Stokes equations,which can well predict the compression-expansion wave structures and wave speed compared with experimental results and can be applied to the simulation of the flow control by using NSDBD.The model is adopted to investigate the separation control over NACA0015 airfoil using the NSDBD plasma actuator.The separation-control mechanisms are revealed that the spanwise vortices produced by the plasma actuation play the key role.Each plasma actuation can produce a spanwise vortex around the separation point near the leading edge.The spanwise vortices make the separated free-shear layer unstable and shed away,move downstream along the upper wall,control the flow near the wall,and bring outer flow with high kinetic energy into the near wall region to realize the effective separation control over the upper surface of the airfoil.展开更多
Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase （fLuc） for bioluminescence imaging or the HSV1 thymidine kinase （HSV1-TK） for radiopharmaceutical-based imagin...Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase （fLuc） for bioluminescence imaging or the HSV1 thymidine kinase （HSV1-TK） for radiopharmaceutical-based imaging were constructed to monitor human embryonic stem cell （hESC） engraftment and proliferation in live mice after trans- plantation. The constitutive expression of either transgene did not alter the properties of hESCs in the culture. We next monitored the formation of teratomas in SCID mice to test （1） whether the gene-modified hESCs maintain their developmental pluripotency, and （2） whether sustained reporter gene expression allows noninvasive, whole-body imaging of hESC derivatives in a live mouse model. We observed teratoma formation from both types of gene-modified cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical imaging system, bioluminescence from the fLuc-transduced hESCs was easily detected in mice bearing teratomas long before palpable tumors could be detected. To develop a noninvasive imaging method more readily translatable to the clinic, we also utilized HSV1-TK and its specific substrate, 1-（2＇-deoxy-2＇-fluoro-β-D-arabinofuranosyl）-5-[^125I]iodouracil（[^125I]FIAU）, as a reporter/ probe pair. After systemic administration, [^125I]FIAU is phosphorylated only by the transgene-encoded HSV1-TK enzyme and retained within transduced （and transplanted） cells, allowing sensitive and quantitative imaging by single-photon emission computed tomography. Noninvasive imaging methods such as these may enable us to monitor the presence and distribution of transplanted human stem cells repetitively within live recipients over a long term through the expression of a reporter gene.展开更多
We previously showed that Wnt3a could stimulate human embryonic stem （hES） cell proliferation and affect cell fate determination. In the absence of feeder cell--derived factors, hES cells cultured under a feeder-fre...We previously showed that Wnt3a could stimulate human embryonic stem （hES） cell proliferation and affect cell fate determination. In the absence of feeder cell--derived factors, hES cells cultured under a feeder-free condition survived and proliferated poorly. Adding recombinant Wnt3a in the absence of feeder cell derived-factors stimulated hES cell proliferation but also differentiation. In the present study, we further extended our analysis to other Wnt ligands such as Wntl and Wnt5a. While Wntl displayed a similar effect on hES cells as Wnt3a, Wnt5a had little effect in this system. Wnt3a and Wntl enhanced proliferation of undifferentiated hES cells when feeder-derived self-renewal factors and bFGF are also present. To explore the possibility to promote the proliferation of undifferentiated hES cells by activating the Wnt signaling, we overexpressed Wnt3a or Wntl gene in immortalized human adult fibroblast （HAFi） cells that are superior in supporting long-term growth of undifferentiated hES cells than primary mouse embryonic fibroblasts. HAFi cells with or without a Wnt tmnsgene can be propagated indefinitely. Over-expression of the Wnt3a gene significantly enhanced the ability of HAFi feeder cells to support the undifferentiated growth of 3 different hES cell lines we tested. Co-expression of three commonly-used drug selection genes in Wnt3a-overpressing HAFi cells further enabled us to select rare hES clones after stable transfection or transduction. These immortalized engineered feeder cells （W3R） that co-express growth-promoting genes such as Wnt3a and three drug selection genes should empower us to efficiently make genetic modified hES cell lines for basic and translational research.展开更多
Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammali...Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.展开更多
Developing an intracellular delivery system is of key importance in the expansion of protein-based therapeutics acting on cytosolic or nuclear targets.Recently,extracellular vesicles(EVs)have been exploited as next-ge...Developing an intracellular delivery system is of key importance in the expansion of protein-based therapeutics acting on cytosolic or nuclear targets.Recently,extracellular vesicles(EVs)have been exploited as next-generation delivery modalities due to their natural role in intercellular communication and biocompatibility.However,fusion of protein of interest to a scaffold represents a widely used strategy for cargo enrichment in EVs,which could compromise the stability and functionality of cargo.Herein,we report intracellular delivery via Ev-based approach(IDEA)that efficiently packages and delivers native proteins both in vitro and in vivo without the use of a scaffold.As a proof-of-concept,we applied the IDEA to deliver cyclic GMP-AMP synthase(cGAS),an innate immune sensor.The results showed that cGAS-carrying EVs activated interferon signaling and elicited enhanced antitumor immunity in multiple syngeneic tumor models.Combining cGAS EVs with immune checkpoint inhibition further synergistically boosted antitumor efficacy in vivo.Mechanistically,scRNA-seq demonstrated that cGAS EVs mediated significant remodeling of intratumoral microenvironment,revealing a pivotal role of infiltrating neutrophils in the antitumor immune milieu.Collectively,IDEA,as a universal and facile strategy,can be applied to expand and advance the developmentof protein-based therapeutics.展开更多
Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbio...Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.展开更多
Research on doping modification of ZnTiO_(3) ceramics to enhance microwave dielectric properties has been hindered by poor performance,unclear structure-function mechanisms.To expand the applicability of ZnTiO_(3) cer...Research on doping modification of ZnTiO_(3) ceramics to enhance microwave dielectric properties has been hindered by poor performance,unclear structure-function mechanisms.To expand the applicability of ZnTiO_(3) ceramics,this study explores Zn_(1-x)Li_(2x)TiO_(3)(O≤×≤1)ceramics using a phase engineering strategy.Our findings reveal that the introduction of Lit into the ZnTiO_(3) system initiates a multiple phase transition,starting at x=0.1.Initially,ilmenite ZnTiO_(3) transforms into a cubic ordered spinel phase(space group P4332).Subsequently,a transition to a disordered spinel phase(space group Fd3m)occurs at x=0.5,culminating in the formation of a monoclinic rock salt-structured LizTiO3 phase.Significantly,two sets of ceramics with near-zero temperature coefficients of resonance frequency(t:)were obtained at x=0.1 and 0.75.Moreover,the quality factor(Qxf)demonstrated a 4.4-fold increase compared to that of ZnTiO_(3) ceramics at x=0.25(105,013 GHz).Additionally,it was observed that the Ti4 polarization in Zn_(1-x)Li_(2x)TiO_(3) ceramics was underestimated by 11.3%-13.3%,causing the measured dielectric constant(e.)exceeding the theoretical dielectric constant(eth).The ionic polarizability of Ti*was adjusted to stabilize around 3.29 A.Evaluation using multiple methods,including Phillips-van Vechten-Levine(P-V-L)theory,Raman vibrational mode analysis,bond valence,bond energy theory,and octahedral distortion,confirms that the Ti-O bonds within the octahedron predominantly affect&r,the increasing lattice energy(U)contributes to the enhancement of Qxf,and the strengthened Li-O bond energy effectively regulates Tr.展开更多
The study of plant species abundance distribution(SAD)in natural communities is of considerable importance to understand the processes and ecological rules of community assembly.With the distribution of tree,shrub and...The study of plant species abundance distribution(SAD)in natural communities is of considerable importance to understand the processes and ecological rules of community assembly.With the distribution of tree,shrub and herb layers of eight natural communities of Toona ciliata as research targets,three diff erent ecological niche models were used:broken stick model,overlapping niche model and niche preemption model,as well as three statistical models:log-series distribution model,log-normal distribution model and Weibull distribution model,to fi t SAD of the diff erent vegetation layers based on data collected.Goodness-of-fi t was compared with Chi square test,Kolmogorov–Smirnov(K–S)test and Akaike Information Criterion(AIC).The results show:(1)based on the criteria of the lowest AIC value,Chi square value and K–S value with no signifi cant diff erence(p>0.05)between theoretic and observed SADs.The suitability and goodness-of-fi t of the broken stick model was the best of three ecological niche models.The log-series distribution model did not accept the fi tted results of most vegetation layers and had the lowest goodness-of-fi t.The Weibull distribution model had the best goodness-of-fi t for SADs.Overall,the statistical SADs performed better than the ecological ones.(2)T.ciliata was the dominant species in all the communities;species richness and diversity of herbs were the highest of the vegetation layers,while the diversities of the tree layers were slightly higher than the shrub layers;there were fewer common species and more rare species in the eight communities.The herb layers had the highest community evenness,followed by the shrub and the tree layers.Due to the complexity and habitat diversity of the diff erent T.ciliata communities,comprehensive analyses of a variety of SADs and tests for optimal models together with management,are practical steps to enhance understanding of ecological processes and mechanisms of T.ciliata communities,to detect disturbances,and to facilitate biodiversity and species展开更多
Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）,...Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.展开更多
A great deal of research and practical production indicated that a perfectshape control system needs a precise prediction model of roll wear. According to the practical wearcurve of work roll in Angang ASP1700 hot str...A great deal of research and practical production indicated that a perfectshape control system needs a precise prediction model of roll wear. According to the practical wearcurve of work roll in Angang ASP1700 hot strip mill, which was measured by a roll-profilemeter, themodel of wear curve caused by one single strip was established. The prediction of work-roll wear wasachieved by combining Fortran language and practical technology parameters. The calculated resultsagreed well with the measured.展开更多
Human embryonic stem (ES) cells are capable of unlimited proliferation and maintenance of pluripo-tency in vitro;these properties may lead to potential applications in regenerative medicine. However,immune rejection h...Human embryonic stem (ES) cells are capable of unlimited proliferation and maintenance of pluripo-tency in vitro;these properties may lead to potential applications in regenerative medicine. However,immune rejection hampers the allogenic application of human ES cells. Over-expression of several specific transcription factors has been used to reprogram human adult cells into induced pluripotent stem (iPS) cells,which are similar to hESCs in many aspects. The iPS technique makes it possible to produce patient-specific pluripotent stem cells for transplantation therapy without immune rejection. However,some challenges remain,including viral vector integration into the genome,the existence of exogenous oncogenic factors,and low induction efficiency. Here,we review recent advances in human iPS methodology,as well as remaining challenges and its potential applications.展开更多
Two papers [1, 2] published in a recent issue of Cell Research describe the derivation of pluripotent human embryonic stem （hES）-like cell lines from parthenogeneic blastocysts.
Gene targeting is the method of precise genome modification that utilizes the innate DNA repair mechanism in cells, known as homologous recombination. At its genesis, gene targeting in mouse embryonic stem （ES） cell...Gene targeting is the method of precise genome modification that utilizes the innate DNA repair mechanism in cells, known as homologous recombination. At its genesis, gene targeting in mouse embryonic stem （ES） cells was a breakthrough for genetics and developmental biology. Its application has enhanced researchers＇ ability to study gene function and model human disease, which was recognized by the Nobel Prize in Physiology or Medicine 2007.展开更多
Dear editor,The 2019 novel coronavirus(later renamed as SARS-CoV-2 in February 2020)infected over 12 million people globally by early July 2020,causing mild to severe COVID-19 in millions.Monitoring the levels of anti...Dear editor,The 2019 novel coronavirus(later renamed as SARS-CoV-2 in February 2020)infected over 12 million people globally by early July 2020,causing mild to severe COVID-19 in millions.Monitoring the levels of antibodies such as immunoglobin(Ig)G,M and A that are specific to SARS-CoV-2 and present in the blood provides not only an alternative method for diagnosing SARS-CoV-2 infection(including asymptomatic carriers),but also a simple way to monitor immune responses in convalescent patients or after vaccination.A high and persistent level of antibodies specific to SARS-CoV-2,especially those that can bind to and neutralize the virus,would be a strong indication that an immunized host could resist to SRAS-CoV-2 infection.Currently,there are no effective drugs to specifically prevent or cure SARS-CoV-2 infection;therefore,host immune responses and antibody-based therapeutics will continue to play important roles in combating and later preventing COVID-19.展开更多
With great sadness,we residing in China heard the news that Professor Hal E.Broxmeyer passed away on December 8,2021,due to complications of thyroid cancer.He was 77.We regret that we could not say goodbye in person t...With great sadness,we residing in China heard the news that Professor Hal E.Broxmeyer passed away on December 8,2021,due to complications of thyroid cancer.He was 77.We regret that we could not say goodbye in person to Hal,as he was fondly called by his students and colleagues around the world.We wish to express publicly our heartfelt gratitude to Hal for his many seminal contributions to the scientific research and applications,and profound impact on the careers of younger scientists like us.We are sure that our feeling and gratitude are also shared by hundreds of youngsters who are fortunate to have interactions with Hal.He will continue to be a bright star in the sky,inspiring and guiding us for many years to come.展开更多
基金We acknowledge funding support from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29030104)National Natural Science Foundation of China(Grant Nos.:31870731 and U1732109)+2 种基金the Fundamental Research Funds for the Central Universities(WK2070000108)a COVID-19 special task grant supported by Chinese Academy of Science Clinical Research Hospital(Hefei)(YD2070002017 and YD2070002001)the new medical science fund of USTC(WK2070000130).
文摘Currently,detecting SARS-CoV-2 RNAs is a standard approach for COVID-19 diagnosis.However,there is an urgent need for reliable and rapid serological diagnostic methods to screen SARS-CoV-2-infected people including those who do not have overt symptoms.Most emerging studies described serological tests based on detection of SARS-CoV-2-specific IgM and IgG.1–4 Although detection of SARS-CoV-2-specific IgA in serum has been reported in few papers,5,6 analyses of IgA levels in a larger number of COVID-19 patients are still lacking.
基金Supported by the Basic Research Programs of Applied Science and Technology Commission Foundation of Gansu Province, No. QS 031-c33-05
文摘AIM: Human heparanase is an endo-D-glucuronidase that degrades heparan sulfate/heparin and has been implicated in a variety of biological processes. The objective was to investigate the expression of heparanase (Hps) and basic fibroblast growth factor (bFGF) and their relationship to neoangiogenesis and metastasis of human esophageal carcinoma.METHODS: Seventy-nine patients who had undergone esophageal resection for esophageal carcinoma without preoperative treatment were included in the present study. Immunohistochemistry was used to study the expression of Hps, bFGF and microvessel density (MVD) in 79 cases of esoph-ageal carcinoma. bFGF and Hps were quantitatively detected with immunohistochemistry in 79 cases of human esopha-geal carcinoma and 19 cases of adjacent normal human esophageal carcinoma. Cd34 was used to explore the MVD as a marker of endothelial cells. RESULTS: Hps and bFGF expression in tumor tissue, being remarkably higher than that in normal esophageal tissue, were significantly correlated with clinicopathological features (depth of invasion, lymph-node metastasis and TNM stage) and MVD.CONCLUSION: The results of this study suggest that thecoexpression of Hps and bFGF plays a key role in angiogenesis, invasion and metastasis of esophageal carcinoma. Hps and bFGF may serve as a predictor of progression in esophageal carcinoma. The expression of heparanase in esophageal carcinoma enhances growth, invasion, and angiogenesis of the tumor, and bFGF seemsto be a potent antigenic factor for esophageal carcinoma.
基金This work was supported by the‘973'ScienceTechnology Development Plan of the National Basic Research Foundation(No.1998061500)the 985'Foundation of Tsinghua University.
文摘3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is lower bainite plates or polygonal ferrite containing quantities of dispersed cementite particles, mixed with a few of low carbon martensite laths or ferrite, depending on the heat input. The hardness and the tensile strength of the weld metal are higher than those of the base metal, and monotonously increase as the heat input decreases. No softened zone exists in heat affected zone (HAZ). Compared with the base metal, although the grains of laser weld are much larger, the toughness of the weld metal is higher within a large range of heat input. Furthermore, as the heat input increases, the toughness of the weld metal rises to a maximum value, at which point the percentage of lower bainite is the highest, and then drops.
基金supported by the National Natural Science Foundation of China(Grant Nos.10972236,50906100)
文摘In order to simulate the flow control problem by using Nanosecond Pulsed Dielectric Barrier Discharge(NSDBD),a one-zone inhomogeneous phenomenological model is constructed based on the experimental and theoretical results.The model is coupled with the unsteady Navier-Stokes equations,which can well predict the compression-expansion wave structures and wave speed compared with experimental results and can be applied to the simulation of the flow control by using NSDBD.The model is adopted to investigate the separation control over NACA0015 airfoil using the NSDBD plasma actuator.The separation-control mechanisms are revealed that the spanwise vortices produced by the plasma actuation play the key role.Each plasma actuation can produce a spanwise vortex around the separation point near the leading edge.The spanwise vortices make the separated free-shear layer unstable and shed away,move downstream along the upper wall,control the flow near the wall,and bring outer flow with high kinetic energy into the near wall region to realize the effective separation control over the upper surface of the airfoil.
文摘Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase （fLuc） for bioluminescence imaging or the HSV1 thymidine kinase （HSV1-TK） for radiopharmaceutical-based imaging were constructed to monitor human embryonic stem cell （hESC） engraftment and proliferation in live mice after trans- plantation. The constitutive expression of either transgene did not alter the properties of hESCs in the culture. We next monitored the formation of teratomas in SCID mice to test （1） whether the gene-modified hESCs maintain their developmental pluripotency, and （2） whether sustained reporter gene expression allows noninvasive, whole-body imaging of hESC derivatives in a live mouse model. We observed teratoma formation from both types of gene-modified cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical imaging system, bioluminescence from the fLuc-transduced hESCs was easily detected in mice bearing teratomas long before palpable tumors could be detected. To develop a noninvasive imaging method more readily translatable to the clinic, we also utilized HSV1-TK and its specific substrate, 1-（2＇-deoxy-2＇-fluoro-β-D-arabinofuranosyl）-5-[^125I]iodouracil（[^125I]FIAU）, as a reporter/ probe pair. After systemic administration, [^125I]FIAU is phosphorylated only by the transgene-encoded HSV1-TK enzyme and retained within transduced （and transplanted） cells, allowing sensitive and quantitative imaging by single-photon emission computed tomography. Noninvasive imaging methods such as these may enable us to monitor the presence and distribution of transplanted human stem cells repetitively within live recipients over a long term through the expression of a reporter gene.
文摘We previously showed that Wnt3a could stimulate human embryonic stem （hES） cell proliferation and affect cell fate determination. In the absence of feeder cell--derived factors, hES cells cultured under a feeder-free condition survived and proliferated poorly. Adding recombinant Wnt3a in the absence of feeder cell derived-factors stimulated hES cell proliferation but also differentiation. In the present study, we further extended our analysis to other Wnt ligands such as Wntl and Wnt5a. While Wntl displayed a similar effect on hES cells as Wnt3a, Wnt5a had little effect in this system. Wnt3a and Wntl enhanced proliferation of undifferentiated hES cells when feeder-derived self-renewal factors and bFGF are also present. To explore the possibility to promote the proliferation of undifferentiated hES cells by activating the Wnt signaling, we overexpressed Wnt3a or Wntl gene in immortalized human adult fibroblast （HAFi） cells that are superior in supporting long-term growth of undifferentiated hES cells than primary mouse embryonic fibroblasts. HAFi cells with or without a Wnt tmnsgene can be propagated indefinitely. Over-expression of the Wnt3a gene significantly enhanced the ability of HAFi feeder cells to support the undifferentiated growth of 3 different hES cell lines we tested. Co-expression of three commonly-used drug selection genes in Wnt3a-overpressing HAFi cells further enabled us to select rare hES clones after stable transfection or transduction. These immortalized engineered feeder cells （W3R） that co-express growth-promoting genes such as Wnt3a and three drug selection genes should empower us to efficiently make genetic modified hES cell lines for basic and translational research.
文摘Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.
基金supported by funds from the University of Science and Technology of Chinathe National Natural Science Foundation of China (82250710171, 82100243)+2 种基金USTC Research Funds of the Double FirstClass Initiative (YD9110002034, WK9100000008)partly supported by the Joint Laboratory of Innovation in Life Sciences from the University of Science and Technology of China (USTC)Changchun Zhuoyi Biological Co. Ltd
文摘Developing an intracellular delivery system is of key importance in the expansion of protein-based therapeutics acting on cytosolic or nuclear targets.Recently,extracellular vesicles(EVs)have been exploited as next-generation delivery modalities due to their natural role in intercellular communication and biocompatibility.However,fusion of protein of interest to a scaffold represents a widely used strategy for cargo enrichment in EVs,which could compromise the stability and functionality of cargo.Herein,we report intracellular delivery via Ev-based approach(IDEA)that efficiently packages and delivers native proteins both in vitro and in vivo without the use of a scaffold.As a proof-of-concept,we applied the IDEA to deliver cyclic GMP-AMP synthase(cGAS),an innate immune sensor.The results showed that cGAS-carrying EVs activated interferon signaling and elicited enhanced antitumor immunity in multiple syngeneic tumor models.Combining cGAS EVs with immune checkpoint inhibition further synergistically boosted antitumor efficacy in vivo.Mechanistically,scRNA-seq demonstrated that cGAS EVs mediated significant remodeling of intratumoral microenvironment,revealing a pivotal role of infiltrating neutrophils in the antitumor immune milieu.Collectively,IDEA,as a universal and facile strategy,can be applied to expand and advance the developmentof protein-based therapeutics.
基金supported by the China Postdoctoral Science Foundation(2020M671373)Jiangsu Postdoctoral Research Funding Program(2020Z070)+2 种基金Jiangsu Agriculture Science and Technology Innovation Fund(CX(20)2036)Key Research and Development Project of Jiangsu Province(BE2020314)Innovation Training Program for College Students(202310299649X).
文摘Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.
基金This work was supported by the National Natural Science Foundation of China(No.52102129)the Hunan Provincial Natural Science Foundation of China(No.2023JJ30138)the science and technology innovation Program of Hunan Province(No.2023RC3094).
文摘Research on doping modification of ZnTiO_(3) ceramics to enhance microwave dielectric properties has been hindered by poor performance,unclear structure-function mechanisms.To expand the applicability of ZnTiO_(3) ceramics,this study explores Zn_(1-x)Li_(2x)TiO_(3)(O≤×≤1)ceramics using a phase engineering strategy.Our findings reveal that the introduction of Lit into the ZnTiO_(3) system initiates a multiple phase transition,starting at x=0.1.Initially,ilmenite ZnTiO_(3) transforms into a cubic ordered spinel phase(space group P4332).Subsequently,a transition to a disordered spinel phase(space group Fd3m)occurs at x=0.5,culminating in the formation of a monoclinic rock salt-structured LizTiO3 phase.Significantly,two sets of ceramics with near-zero temperature coefficients of resonance frequency(t:)were obtained at x=0.1 and 0.75.Moreover,the quality factor(Qxf)demonstrated a 4.4-fold increase compared to that of ZnTiO_(3) ceramics at x=0.25(105,013 GHz).Additionally,it was observed that the Ti4 polarization in Zn_(1-x)Li_(2x)TiO_(3) ceramics was underestimated by 11.3%-13.3%,causing the measured dielectric constant(e.)exceeding the theoretical dielectric constant(eth).The ionic polarizability of Ti*was adjusted to stabilize around 3.29 A.Evaluation using multiple methods,including Phillips-van Vechten-Levine(P-V-L)theory,Raman vibrational mode analysis,bond valence,bond energy theory,and octahedral distortion,confirms that the Ti-O bonds within the octahedron predominantly affect&r,the increasing lattice energy(U)contributes to the enhancement of Qxf,and the strengthened Li-O bond energy effectively regulates Tr.
基金Hubei Provincial Department of Science and Technology,under the public welfare research project[No.402012DBA40001]Hubei Provincial Department of Education,under the scientifi c research project[No.B20160555].
文摘The study of plant species abundance distribution(SAD)in natural communities is of considerable importance to understand the processes and ecological rules of community assembly.With the distribution of tree,shrub and herb layers of eight natural communities of Toona ciliata as research targets,three diff erent ecological niche models were used:broken stick model,overlapping niche model and niche preemption model,as well as three statistical models:log-series distribution model,log-normal distribution model and Weibull distribution model,to fi t SAD of the diff erent vegetation layers based on data collected.Goodness-of-fi t was compared with Chi square test,Kolmogorov–Smirnov(K–S)test and Akaike Information Criterion(AIC).The results show:(1)based on the criteria of the lowest AIC value,Chi square value and K–S value with no signifi cant diff erence(p>0.05)between theoretic and observed SADs.The suitability and goodness-of-fi t of the broken stick model was the best of three ecological niche models.The log-series distribution model did not accept the fi tted results of most vegetation layers and had the lowest goodness-of-fi t.The Weibull distribution model had the best goodness-of-fi t for SADs.Overall,the statistical SADs performed better than the ecological ones.(2)T.ciliata was the dominant species in all the communities;species richness and diversity of herbs were the highest of the vegetation layers,while the diversities of the tree layers were slightly higher than the shrub layers;there were fewer common species and more rare species in the eight communities.The herb layers had the highest community evenness,followed by the shrub and the tree layers.Due to the complexity and habitat diversity of the diff erent T.ciliata communities,comprehensive analyses of a variety of SADs and tests for optimal models together with management,are practical steps to enhance understanding of ecological processes and mechanisms of T.ciliata communities,to detect disturbances,and to facilitate biodiversity and species
基金supported by NIH R01 DE14190(HX),R21 DE22625(HX)and R01 HL-073781(LC)the University of Maryland School of Dentistry startup fund(HX)
文摘Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.
文摘A great deal of research and practical production indicated that a perfectshape control system needs a precise prediction model of roll wear. According to the practical wearcurve of work roll in Angang ASP1700 hot strip mill, which was measured by a roll-profilemeter, themodel of wear curve caused by one single strip was established. The prediction of work-roll wear wasachieved by combining Fortran language and practical technology parameters. The calculated resultsagreed well with the measured.
基金Supported by the National Key Scientific Program (Grant Nos.2007CB947960,2007CB948003)
文摘Human embryonic stem (ES) cells are capable of unlimited proliferation and maintenance of pluripo-tency in vitro;these properties may lead to potential applications in regenerative medicine. However,immune rejection hampers the allogenic application of human ES cells. Over-expression of several specific transcription factors has been used to reprogram human adult cells into induced pluripotent stem (iPS) cells,which are similar to hESCs in many aspects. The iPS technique makes it possible to produce patient-specific pluripotent stem cells for transplantation therapy without immune rejection. However,some challenges remain,including viral vector integration into the genome,the existence of exogenous oncogenic factors,and low induction efficiency. Here,we review recent advances in human iPS methodology,as well as remaining challenges and its potential applications.
文摘Two papers [1, 2] published in a recent issue of Cell Research describe the derivation of pluripotent human embryonic stem （hES）-like cell lines from parthenogeneic blastocysts.
文摘Gene targeting is the method of precise genome modification that utilizes the innate DNA repair mechanism in cells, known as homologous recombination. At its genesis, gene targeting in mouse embryonic stem （ES） cells was a breakthrough for genetics and developmental biology. Its application has enhanced researchers＇ ability to study gene function and model human disease, which was recognized by the Nobel Prize in Physiology or Medicine 2007.
基金T.J.is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29030104)National Natural Science Foundation of China(31870731 and U1732109)+3 种基金the Fundamental Research Funds for the Central Universities(WK2070000108)a COVID-19 special task grant supported by Chinese Academy of Sciences Clinical Research Hospital(Hefei)with Grant No.YD2070002017M.H.is supported by the new medical science fund of University of Science and Technology of China(WK2070000130)J.W.and X.Y.are supported by the Fundamental Research Funds for the Central Universities with Grant Nos.YD9110004001 and YD9110002002,respectively.
文摘Dear editor,The 2019 novel coronavirus(later renamed as SARS-CoV-2 in February 2020)infected over 12 million people globally by early July 2020,causing mild to severe COVID-19 in millions.Monitoring the levels of antibodies such as immunoglobin(Ig)G,M and A that are specific to SARS-CoV-2 and present in the blood provides not only an alternative method for diagnosing SARS-CoV-2 infection(including asymptomatic carriers),but also a simple way to monitor immune responses in convalescent patients or after vaccination.A high and persistent level of antibodies specific to SARS-CoV-2,especially those that can bind to and neutralize the virus,would be a strong indication that an immunized host could resist to SRAS-CoV-2 infection.Currently,there are no effective drugs to specifically prevent or cure SARS-CoV-2 infection;therefore,host immune responses and antibody-based therapeutics will continue to play important roles in combating and later preventing COVID-19.
文摘With great sadness,we residing in China heard the news that Professor Hal E.Broxmeyer passed away on December 8,2021,due to complications of thyroid cancer.He was 77.We regret that we could not say goodbye in person to Hal,as he was fondly called by his students and colleagues around the world.We wish to express publicly our heartfelt gratitude to Hal for his many seminal contributions to the scientific research and applications,and profound impact on the careers of younger scientists like us.We are sure that our feeling and gratitude are also shared by hundreds of youngsters who are fortunate to have interactions with Hal.He will continue to be a bright star in the sky,inspiring and guiding us for many years to come.
